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Seite 1 von 3 Bonn, 30. März 2010 Comments of German Medicines Manufacturers Association on the GHTF Discussion Paper (in view of preparation of a draft guidance on) „UDI for Medical Devices” The BAH – German Medicines Manufacturers' Association represents the interests of the pharmaceutical industry towards the German Federal Government, the German Bundestag and the German Bundesrat. With its more than 450 members, BAH is the largest association in terms of members in the German pharmaceutical sector. Because those medicines without pharmacological effect [e.g. rinsing solutions e.g. for the nose or the bladder; healing earths, fango paraffins, (thermotherapy) hyaluronic acid for intra-articular injection („joint lubricant")] became medical devices the BAH founded a medical devices section and a dental section (for producers of dental restorative materials). Part A: General comments on the UDI System 1. It is to be welcomed that this topic is being addressed on a global level. However, a new system must bring quantifiable benefits in excess of the costs involved and the arguments to justify a UDI System are not presented. It is unlikely that Governments can allocate funds for setting up and maintaining the database and therefore the main costs will lie with medical device manufacturers. Manufacturers must pass these costs on (in whole or in part) to customers. The result is that worldwide treatment costs for patients will rise. An unfair proportion falls on „poorer” markets, who will not benefit from UDI. Therefore the database should be as simple as possible. Without an evidence-based approach the costs of UDI cannot be justified and the hoped-for benefits will not be realised. 2. In order to achieve a higher protection against falsified medical devices there is a need to include all parties involved. The now proposed UDI System only involves hospitals as end-users (cf. UDI Storyboard, page 13). Surgeries, dental surgeries, pharmacies, distributors, brokers, traders, agents, wholesalers and retail seller are not taken into consideration. An all-over protection against counterfeits needs to respect this parties. Seite 2 von 3 Part B: Specific comments on the Discussion Paper 1. Concerning item 2.2 „Purpose” (page 5): a. „improve patient safety by reducing device related medical errors” Evidence of the current experience of device related medical errors must be presented, in comparison to other types of medical errors. An analysis must show whether the level of device related medical errors is unacceptable, and whether they occur significantly more often in particular types of medical devices. It must be shown whether UDI would have eliminated the error, in comparison to other possible activities. In the dental industry we do not have evidence that device related medical errors occur. We recommend that UDI is limited to those device groups which currently have an unacceptable level of device related medical errors, and where UDI can actually achieve an improvement. Furthermore, by definition, low risk devices (EU MDD Class 1) pose little risk for patients. Therefore, unless there is evidence of unacceptable, widespread and serious problems concerning adverse events with Class 1 devices, there are currently no problems concerning patient safety. The primary goal of UDI is therefore not applicable for Class 1 devices and therefore all Class 1 medical devices should be excluded from UDI. b. „improving patient safety by enhancing the identification of devices in case of adverse events” This goal is imprecise and must identify which existing problems will be solved through implementation of UDI. When the problems lie in terms of communication between regulatory authorities, it must be shown that UDI is the answer. c. „facilitating traceability” This goal is perhaps the one must likely to be realised, when redefined as „hindering counterfeiting of devices”. Traceability is a current requirement of Quality System and MDD regulation and UDI does not change or add to this. Stakeholders can identify the responsible manufacturer by reading the labelling and the batch number enables the manufacturer to identify the production records. Therefore, when the stakeholder has the device, then traceability is already possible and will not be improved through UDI. Seite 3 von 3 What could be meant is; „enables devices to be located, at any point in the supply chain”. Counterfeit products would not have the right „history” and the stakeholder could identify that the device is not authorised. Supply companies would be required to log the progress of UDI devices through their hands and hospitals and medical professionals could access the database as a routine check on receiving the goods, or in those situations where they doubt the origin of the device. Once again, an analysis is necessary to identify which medical device groups suffer from counterfeiting and require measures to be taken. Certain medical device groups might be excluded altogether and the priority could be set according to risk. Building UDI to focus on reducing counterfeiting of medical devices would have the benefit of bringing the financial rewards to those most likely to carry the main costs (manufacturers). 2. Concerning item 8. „UDI Database”(page 10) Concerning the suggestion that “Each jurisdiction shall establish its UDID (...)” this would mean that a EU UDID should be set up. To minimise the burden a company should only be expected to submit data once – presumably in the country where they are based and therefore all potential stakeholders worldwide would need to have access the information in the EU UDID. Each core identification attribute in the proposed UDID database should be critically reviewed and only those which are absolutely necessary included. The requirement for data which is “nice to have” should be avoided, due to the costs involved in entering and maintaining each data item e.g. quantity and packaging level, size including units of measures, labelled as single use, sterility, sterilization before use, restricted number of use, containing allergens, regional authorised representatives and special instructions or use should be removed. These items are already indicated in the labelling in human-readable form and it therefore brings no benefit to add them to a database too. Dr. Angela Josewski

GHTF/AHWG-UDI/N2R3:2011 FINAL DOCUMENT Global Harmonization Task Force Title: Unique Device Identification (UDI) System for Medical Devices Authoring Group: GHTF SC UDI Ad Hoc Working Group Endorsed by: The Global Harmonization Task Force Date: September 16, 2011 Dr. Kazunari Asanuma, GHTF Chair This document was produced by the Global Harmonization Task Force, a voluntary international group of representatives from medical device regulatory authorities and trade associations from Europe, the United States of America (USA), Canada, Japan and Australia. The document is intended to provide non-binding guidance to regulatory authorities for use in the regulation of medical devices, and has been subject to consultation throughout its development. There are no restrictions on the reproduction, distribution or use of this document; however, incorporation of this document, in part or in whole, into any other document, or its translation into languages other than English, does not convey or represent an endorsement of any kind by the Global Harmonization Task Force. Copyright © 2011 by the Global Harmonization Task Force Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 2 of 13 TABLE OF CONTENTS 1.0 Introduction 2.0 Rational, Purpose and Scope 3.0 References 4.0 Definitions 5.0 Guidance for a UDI System 6.0 The UDI 7.0 The UDI Carrier 8.0 The UDI Database Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 3 of 13 Preamble This document was produced by the Global Harmonization Task Force, a voluntary group of representatives from medical device regulatory agencies and the regulated industry. The document is intended to provide non-binding guidance for use in the regulation of medical devices, and has been subject to consultation throughout its development. There are no restrictions on the reproduction, distribution or use of this document; however, incorporation of this document, in part or in whole, into any other document, or its translation into languages other than English, does not convey or represent an endorsement of any kind by the Global Harmonization Task Force. 1. Introduction This purpose of this guidance is to provide a framework for those regulatory authorities that intend to develop their own UDI Systems – such that, when implemented, we achieve a globally harmonized approach to UDI. We expect the regulatory authorities to follow the guidance when developing their own UDI requirements. The framework can be used at a local, national, or global level. In order to reach the goal of a global UDI System, it is critical that these systems are implemented without regional or national differences. This guidance is intended to provide a high-level conceptual view of how a global UDI System should work. We recognize that further additional guidance may be needed once these core concepts are implemented. The fundamental concepts of a global UDI System include: • The UDI and UDI Carrier are based on global standards • A UDI applied to a medical device anywhere in the world should be able to be used globally to meet the UDI requirements of any regulatory authority • National or local identification numbers should NOT be a substitute for UDI • Regulatory Authorities should not specify how to modify these standards • The UDI Database core elements should not be modified • The UDI Database should use the HL7 SPL for data exchange The UDI System is intended to provide a single, globally-accepted system for positive identification of medical devices. Health care professionals and patients will no longer have to access multiple, inconsistent, and incomplete sources in an attempt to identify a device, its key attributes. The UDID is a designated source for additional information. It is critical to note that the benefits of UDI can only accrue if all stakeholders, from the manufacturer through to healthcare providers and patients, use UDI throughout their system. Therefore, it Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 4 of 13 is imperative that all stakeholders be educated about the development and use of a UDI System. A globally harmonized and consistent approach to UDI is expected to increase patient safety and help optimize patient care by facilitating the: 1. traceability of devices, especially for recalls and other field service corrective actions, 2. adequate identification of the device through its distribution and use, 3. identification of devices in adverse events, 4. reduction of medical errors, and 5. documentation and longitudinal capture of data on medical devices. 1. Traceability – the global use of a single identifier (UDI) will facilitate traceability throughout distribution. This is especially important for recalls and other field service corrective actions. Though the UDI Database does not capture Production Identifiers, it is expected that supply chain partners will capture and use these identifiers. This is critical during recalls and other field safety corrective actions. In addition, the foundational use of UDI can help fight counterfeiting and secure the supply chain for all stakeholders. Traceability includes: • Record of products from manufacturer to health care provider • Record of use in patients • availability of information for direct patient care (implantables) • record for product recalls • standard way to input device identification into registries 2. Identification – UDI will facilitate the adequate identification of the device through its distribution and use by providing a single, global identifier that can be used to link and integrate existing government, clinical, hospital, and industry databases. UDI should allow for improved procurement, inventory management, and accounting. The existence of a single device identifier to link disparate data bases should allow creative new medical and business applications, and synergy among those applications. 3. Adverse Event Reporting – UDI will allow industry and regulatory authorities to more rapidly identify devices involved in adverse events. UDIs will be available for inclusion in adverse event reports, allowing greater accuracy in reporting, and more rapid aggregation of related reports. Using this information, Health Authorities can more rapidly collate and analyze problem reports and identify the most-appropriate solution to a particular concern. UDIs will also allow more targeted safety alerts, recalls, and other corrective actions on the specific devices that are of concern. Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 5 of 13 4. Medical Errors – by providing rapid and electronic access to critical patient safety information relating to the device, the UDI system may help clinicians more safely select and use the proper device for a patient. UDID data could be downloaded by Healthcare organizations to be used for internal checking of safety related information. 5. Documentation – the use of UDI will facilitate and simplify the documentation of device use in various electronic patient records, including electronic health records and registries. UDI should also enable linkages of device information across various systems and across borders. This could help identify device problems and enhance comparative effectiveness. Other issues that need to be considered for the successful development and implementation of a globally harmonized UDI System include: • A risk-based approach is essential given the huge diversity of the medical devices • Kits, systems and other groups of devices need to be managed appropriately. • The requirements should be phased in over a period of years based on premarket risk class, starting with the highest risk class first, to help to reduce the complexity of implementation. • All supply chain stakeholders will need sufficient time frames to prepare their systems, processes and staff, for the proper use of the UDI system. 2. Rationale, purpose and scope 2.1 Rationale There are currently no global definitions of what constitutes a UDI or UDI System. As a consequence, discrepancies between different national approaches do exist and will most likely increase. Common global UDI requirements would offer significant benefits to manufacturers, users, patients, and regulatory authorities. In addition, eliminating or reducing differences between regulators authorities decreases the cost of gaining regulatory compliance. 2.2 Purpose A UDI unambiguously identifies a manufacturer’s specific medical device. A standardized UDI applied to the device or its label, documented in the UDI Database, and used consistently throughout distribution and use should facilitate a number of patient safety benefits, including: • traceability of devices, • the identification of devices in adverse events reports and other postmarket safety surveillance activities, • recalls and other field safety correction, and • reducing medical errors. Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 6 of 13 This guidance intends to avoid country-specific requirements regarding the core elements of the UDI System by developing common guidance to: • create, use and maintain a unique Device Identifier, • apply a UDI Carrier, • establish the UDI Database, with a defined list of Data Elements, and • use a single data exchange standards. In order to facilitate global traceability, the UDI System should be promoted and used at all levels by all stakeholders, including regulatory authorities, medical device manufacturers, distributors, hospitals, pharmacies, medical professionals, and patients. This document was not intended to directly address the issues associated with counterfeit devices or to enable better control of purchasing. 2.3 Scope This document applies to all products to be placed on the market that fall within the definition of a medical device (including accessories) that appears within the GHTF document "Information Document Concerning the Definition of the Term “Medical Device”". Other products, such as equipment used for servicing or maintenance a medical device (e.g. power cord, circuit board) are exempt from the requirements of this document. 3.0 References GHTF final documents SG1/N29:2005 Information Document Concerning the Definition of the Term “Medical Device” SG1/N43:2005 Labelling for Medical Devices SG1/N055:2009 Definitions of the Terms Manufacturer, Authorized Representative, Distributor and Importer Registration and Listing SG1 (PD)/N65 Registration of Manufacturers and other Parties and Listing of Medical Devices Automatic Identification Manufacturers (AIM) Global – Direct Part Marking http://www.aimglobal.org/technologies/dpm/ 4.0 Definitions Accessories Accessories mean an article intended specifically by its manufacturer to be used together with a specific medical device(s), to enable the medical device to be used in accordance with its intended use. [modified draft GHTF definition – revision SG1 N29/R16: 2005] http://www.aimglobal.org/technologies/dpm/ Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 7 of 13 Automatic Identification and Data Capture (AIDC) AIDC refers to the methods for automatic identifying objects, collecting data about them, and entering the data directly into computer systems. Radio Frequency Identification (RFID) RFID is a technology that uses communication through the use of radio waves to exchange data between a reader and an electronic tag attached to an object, for the purpose of identification. UDI System The UDI System is the framework for the production of a Unique Device Identification (UDI), the application of the UDI on the label or directly on device, and the storage of the DI and additional device related information in a UDI Database. UDI UDI means Unique Device Identification. The UDI is a series of numeric or alphanumeric characters that is created through a globally accepted device identification and coding standard. It allows the unambiguous identification of a specific medical device on the market. The UDI comprises the Device Identifier and Production Identifier. Note: The word "Unique" does not imply serialization of individual production units. Device Identifier (DI) The Device Identifier Is a unique numeric or alphanumeric code specific to a model (or version) of medical device and that is also used as the "access key" to information stored in a UDI Database. Production Identifier (PI) The Production Identifier is a numeric or alphanumeric code that identifies the unit of device production. The different types of Production Identifier(s) include serial number, lot/batch number, manufacturing and/or expiration date. UDI Carrier The UDI Carrier is the means to convey the UDI by using Automatic Identification and Data Capture (AIDC) and, if applicable, its human readable interpretation (HRI). Human Readable Interpretation (HRI) Human Readable Interpretation is a legible interpretation of the data characters encoded in the AIDC symbol. Direct Part Mark (DPM) Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 8 of 13 Direct Part Mark “… is a technology used to produce two different surface conditions on an item. These markings can be created by laser etching, molding, peening, etc.” UDI Database (UDID) The UDI Database contains identifying information and other elements associated with the specific medical device. Kits Kits are a collection of medical products, including medical devices, and other products that are packaged together to achieve a stated intended use, being distributed as a single medical device. This includes procedural packs and convenience kits. Label The Label is written, printed or graphic information provided upon the medical device itself. Where physical constraints prevent this happening, this term includes information provided on the packaging of each unit or on the packaging of multiple devices. [GHTF/SG1/N43:2005] Manufacturer Manufacturer means any natural or legal person1 with responsibility for design and/or manufacture of a medical device with the intention of making the medical device available for use, under his name; whether or not such a medical device is designed and/or manufactured by that person himself or on his behalf by another person(s). [GHTF SG1/N055] This includes Reprocessors and Remanufacturers that take responsibility for the device and reintroduce it into commercial distribution. Own Brand/Private Labelers An Own Brand or Private Labeler relabels a device from a 3rd party with his own name without making any further changes to the device thereby taking responsibility for it as the manufacturer. Packaging Levels Packaging levels means the various levels of device packages that contain a fixed quantity of medical devices, e.g., each, carton, case. This does not include shipping containers such as pallets. 1 The term “person” that appears here includes legal entities such as a corporation, a partnership or an association Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 9 of 13 5. Guidance for the UDI System A UDI System comprises 3 parts - 1. The development of the UDI using a globally accepted standard; 2. The application of that UDI on the label or on the device itself; and 3. The submission of appropriate information to the UDID. In order to facilitate a globally harmonized approach to UDI – it is imperative that: 1. In order to achieve traceability (including recalls), it is necessary to require all stakeholders to capture and store the UDI (DI+PI) through distribution and use. 2. The marking of the UDI should be an additional requirement – it does not replace any other marking or labeling requirements. 3. The manufacturer should create and maintain globally unique UDIs on their medical devices. 4. Once the UDI is established on the device or its package, it should never be changed except in the case of reprocessing, remanufacturing, or relabeling. 5. Only the manufacturer can establish the UDI on the device or its packaging. Reprocessors, remanufacturers, Own Brand/Private Labelers are considered the manufacturer of the reprocessed or remanufactured device – and as such are also subject to these requirements. 6. Internationally accepted coding systems managed by global organizations, such as GS1, HIBCC, and ICCBBA, meet the criteria of the UDI and manufacturers shall be permitted to choose which system to use. These organizations have responsibility for maintaining the global uniqueness of their coding systems. It is imperative that these coding systems be adopted and implemented, without national deviations or changes to these global coding systems. 7. In order to accommodate most methods of labeling, marking, and identifying products, the UDI Carrier should not specify any particular AIDC technology. National or regional regulatory requirements shall not restrict methods of AIDC as this will hinder the establishment of a global UDI System. 8. The National/Regional regulation for UDI System shall include a robust process for evaluating and adjudicating applications for UDI exemptions that would exempt certain device types or package levels (including direct part marking) from being labeled with UDI or specific elements in the UDID. 6. The UDI 1. A UDI shall be assigned to the device itself or its package. Higher levels of packaging shall have their own UDIs. 2. When a UDI is not assigned to the device at the level of its unit of use, then a Unit of Use (UoU) Device Identifier should be assigned, to associate the use of a device with a patient. [for example, a UoU DI would be assigned to an individual electrode when the electrode is distributed in a package of 10 – and lowest level UDI is assigned to that package of 10] 3. Accessories distributed separately need their own UDI. Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 10 of 13 4. Kits should have their own UDI. Note: Jurisdictions may differ in their definition of kit. Individual devices within the kit may not need to have a UDI Carrier as long as the manufacturer can identify the individual devices. 5. The manufacturer assigns the UDI to a device following the relevant coding standard. 6. At a minimum, a new UDI is required whenever there is a change that could lead to misidentification of the device or ambiguity in its traceability, including recalls and other field safety correction, AE reporting, and other postmarket safety surveillance activities. 7. Reprocessors, remanufacturers, Own Brand/Private Labelers should create their own, new UDI for the reprocessed, remanufactured, or relabeled medical device, which will replace the OEM’s UDI where it exists. 8. Reprocessors, remanufacturers, Private (Own Brand) Labelers shall retain record of the Original Equipment Manufacturer’s (OEM) UDI. 9. The UDI contains two parts: the Device Identifier and a Production Identifier. 10. The Device Identifier (e.g., GTIN, LIC, ISBT128) should be globally unique at all levels of packaging. 11. If a lot number, serial number, or expiration date appears on the label, they should be part of the UDI Production Identifier. If there is ALSO a manufacturing date on the label, it does NOT need to be included in the PI. If there are no other PIs, the manufacturing date should be used as the PI. 7. UDI Carrier 1. The UDI Carrier (AIDC and HRI representation of the UDI) shall be on the label of the device, its package, or on the device itself, and on all higher levels of packaging. 2. The UDI Carrier for low risk devices packaged and labelled individually does not need to be on its package but rather on a higher level of packaging, e.g. carton. However, when the user is not expected to have access (e.g., home user) to the higher level of packaging (e.g., carton), the UDI should be on its package. 3. Over the Counter (OTC) devices exclusively for retail Point of Sale (POS) do not need to encode Production Identifiers in AIDC on the point of sale package. 4. No particular AIDC methods should be required by a regulatory authority. Globally accepted AIDC methods based on ISO standards that have been approved by the UDI Standards Development Organization (e.g., GS1 or HIBCC) shall be used. 5. RFID has to comply with open, commercially acceptable, industry standards such as EPC – and be vendor neutral. 6. When AIDC carriers other than the UDI Carrier are part of the product labeling, the UDI Carrier shall be readily identifiable. Carriers not intended to be part of the UDI System, but which serve other purposes, are not subject to the specific UDI requirements/standards. Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 11 of 13 7. If linear bar codes are used, the Device Identifier and the Production Identifier(s) can be concatenated or non-concatenated in two or more bar codes. All parts and elements of the UDI bar code shall be distinguishable and identifiable. 8. If there are significant constraints limiting the use of both AIDC and HRI on the label, the AIDC format shall be favored. However, certain environments or use situations, such as home care, may warrant the use of HRI over AIDC. 9. In case of RFID, a linear or 2D bar code shall also be provided. 10. Medical devices that are reusable should have a permanent UDI Carrier on the device itself. 11. Devices that require reprocessing or sterilization (except SUDs) between patient use and implants should be Direct Part Marked in addition to the UDI on the label of the device or its package. Manufacturers may determine that Direct Part Marking may not be possible or warranted on some devices due to size, design, materials, processing, or performance issues. 12. The UDI Carrier should be readable during normal use and throughout intended life of the device. Exception – for DPM - the intended life of the UDI Carrier shall be stated in the labeling. 13. If the UDI Carrier is readily readable through the device’s package, then the UDI Carrier does not also need to be on the package. 14. A single finished medical device made up of multiple parts that have to be assembled may have the permanent UDI Carrier only on one part. It should be on the device that provides the primary mode of activation. 15. The placement of the UDI Carrier should be done in a way that AIDC method can be accessed during normal operation or storage. 8. The UDI Database All UDID data elements should be mandatory, unless marked optional. “If applicable” means the information is mandatory to be in the UDID if it is on the label. Data elements and their definitions for the UDID are listed below. 1. No product commercial confidential information shall be included in the UDID. 2. The manufacturer is responsible for the initial submission and updates to the identifying information and other device data elements in the UDID. 3. The data in the UDID should be publicly available and free of charge. 4. The presence of the device in the UDID does not mean that the device is authorized in all jurisdictions. 5. The database should allow for the linking of all the packaging levels of the product. 6. The data for new UDIs must be available before the product is put on the market. 7. Manufacturers should update the UDID within 30 days when a change is made to an attribute that does NOT require a new UDI. Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 12 of 13 8. The UDI Database shall use the HL7 Structured Product Labeling (SPL) standard for data exchange. 9. The data should be available forever; though the data could be archived if the device is no longer on the market. 10. The core elements are the minimum elements needed to identify a device through distribution and use. Regional or National UDIDs may contain additional elements; however, these additional elements should be kept to a minimum. The core UDI Data Elements are the following: 1. For every packaging level – the following shall be provided in a related way (for entire packaging hierarchy): • Device Identifier (UDI type (GS1, HIBC, ISBT-128) and code) • Quantity per package configuration: (e.g., each, 10 eaches, 5 shelf packs) • Alternative or additional identifier(s) (if applicable) e.g. GS1, HIBC, or ISBT-128 2. The Unit of Use Device Identifier (if applicable) 3. Manufacturer’s Name 4. Manufacturer’s address and contact information (as represented on the label and/or instruction for use) 5. Authorized Representatives (list of countries) (if required by the local/regional regulatory authority) Information about the regional representative's information such as the address or telephone number, when applicable. Name, Address, Email, Telephone 6. Global Medical Device Nomenclature (GMDN) Preferred code and term 7. Trade Name/Brand Name (if applicable) 8. Device model, reference, or catalogue number (if applicable) 9. How the device is controlled: serial, lot/batch number, and/or expiration date (or manufacturing date) (check boxes) 10. Clinical Size (including Volume, Length, Gauge, Diameter ) (if applicable) – applicable when necessary to identify clinically relevant characteristics of the device such as measurement, size appropriate to the product (e.g. 8F catheter) 11. Additional product Description (optional) – Additional clinically relevant information, e.g., radio-opaque (free text) 12. Storage conditions, as labeled on the product and/or in the IFU (if applicable) – to include temperature range, needs to be refrigerated, relative humidity range, pressure range, avoid direct sunlight 13. Handling conditions (if different than storage conditions), as labeled on the product and/or in the IFU (if applicable) – to include temperature range, needs to be refrigerated, relative humidity range, pressure range, avoid direct sunlight 14. Labeled as single use (Yes/No) 15. Is device packaged sterile (Yes/No) 16. Does it need to be sterilized before use (Yes/No) – if so, then the method of sterilization should be indicated [limited list to be developed] [to be validated with users] Unique Device Identification (UDI) System for Medical Devices GHTF Ad Hoc Working Group Final Document GHTF/AHWG-UDI/N2R3:2011 September 16, 2011 Page 13 of 13 17. Restricted number of reuses (if applicable) 18. Labeled as containing latex (Yes/No) 19. Labeled as containing DEHP (Yes/No) 20. License and/or marketing authorization or registration number (if required by the local regulatory authority) 21. URL for additional information, e.g. electronic IFU (optional) 22. Critical warnings or contraindications (if applicable) – if a particular regulation requires that the label of the device contains a critical warning or contraindication associated with the use of the device [list to be developed]. 1. Introduction 2. Rationale, purpose and scope 2.1 Rationale 2.2 Purpose 2.3 Scope 4.0 Definitions 5. Guidance for the UDI System 6. The UDI 7. UDI Carrier 8. The UDI Database

EMPFEHLUNGEN EMPFEHLUNG DER KOMMISSION vom 5. April 2013 über einen gemeinsamen Rahmen für ein System einmaliger Produktkennzeichnung für Medizinprodukte in der Union (Text von Bedeutung für den EWR) (2013/172/EU) DIE EUROPÄISCHE KOMMISSION — gestützt auf den Vertrag über die Arbeitsweise der Europäischen Union, insbesondere auf Artikel 292, in Erwägung nachstehender Gründe: (1) Die Rückverfolgbarkeit von Medizinprodukten über die gesamte Lieferkette hinweg trägt zur Patientensicherheit bei, weil sie die Vigilanz, die Marktüberwachung und die Transparenz in diesem Bereich erleichtert. (2) Der derzeitige Rechtsrahmen für Medizinprodukte enthält keine besonderen Bestimmungen über die Rückverfolg­ barkeit. Um einem verstärkten ordnungspolitischen An­ satz für die Rückverfolgbarkeit von Medizinprodukten den Weg zu ebnen, ist daher eine Empfehlung erforder­ lich. (3) Der Vorschlag der Europäischen Kommission für eine Verordnung des Europäischen Parlaments und des Rates über Medizinprodukte und zur Änderung der Richtlinie 2001/83/EG, der Verordnung (EG) Nr. 178/2002 und der Verordnung (EG) Nr. 1223/2009 ( 1 ), der am 26. Sep­ tember 2012 angenommen wurde, und der Vorschlag der Europäischen Kommission für eine Verordnung des Europäischen Parlaments und des Rates über In-vitro-Di­ agnostika ( 2 ), der ebenfalls am 26. September 2012 an­ genommen wurde, enthalten Bestimmungen über die Rückverfolgbarkeit von Medizinprodukten und In-vitro- Diagnostika zur Verbesserung von Gesundheit und Si­ cherheit der Patienten. (4) In den Schlussfolgerungen des Rates vom 6. Juni 2011 zur Innovation im Sektor der Medizinprodukte ( 3 ) wer­ den die Kommission und die Mitgliedstaaten aufgefordert, den Fragen der Interoperabilität und Sicherheit im Zu­ sammenhang mit der Integration von Medizinprodukten in e-Health-Systeme, insbesondere personalisierte Ge­ sundheitssysteme, besondere Aufmerksamkeit zu wid­ men. (5) Derzeit werden auf internationaler Ebene bedeutende An­ strengungen unternommen, um zu einem weltweit ein­ heitlichen Ansatz zur Rückverfolgbarkeit zu kommen und ein weltweit anerkanntes System für eine einheitliche Produktkennzeichnung (Unique Device Identifier — UDI) für Medizinprodukte einzurichten. (6) Auf der Grundlage unterschiedlicher nationaler und/oder regionaler Anforderungen an die Rückverfolgbarkeit wur­ den bereits UDI-Mechanismen entwickelt, und es besteht die Gefahr, dass auf diesen Ebenen weitere voneinander abweichende UDI-Mechanismen entwickelt werden. (7) Bestimmte im UDI-Code enthaltene Informationen könn­ ten in Zukunft in die elektronische Patientenakte gemäß der Richtlinie 2011/24/EU des Europäischen Parlaments und des Rates vom 9. März 2011 über die Ausübung der Patientenrechte in der grenzüberschreitenden Gesund­ heitsversorgung ( 4 ) und der digitalen Agenda für Euro­ pa ( 5 ) eingespeist werden — HAT DIE FOLGENDE EMPFEHLUNG ANGENOMMEN: 1. EINLEITUNG Zweck der Empfehlung 1. Die Rückverfolgbarkeit wird derzeit nicht durch die ver­ schiedenen Richtlinien über Medizinprodukte ( 6 ) geregelt, wohl aber in einigen Fällen auf nationaler und/oder regio­ naler Ebene. Die Unterschiede und Unvereinbarkeit der Rückverfolgbarkeitsmechanismen können die Effizienz der Systeme schwächen oder beeinträchtigen. 2. Darüber hinaus würde die Entwicklung unterschiedlicher nationaler und/oder regionaler Produktkennzeichnungs­ mechanismen die Hersteller zwingen, ihre Produkte an je­ den einzelnen Mechanismus anzupassen, um den Anforde­ rungen an die Rückverfolgbarkeit zu genügen. DE 9.4.2013 Amtsblatt der Europäischen Union L 99/17 ( 1 ) KOM(2012) 542 endg. ( 2 ) KOM(2012) 541 endg. ( 3 ) ABl. C 202 vom 8.7.2011, S. 7. ( 4 ) ABl. L 88 vom 4.4.2011, S. 45. ( 5 ) http://ec.europa.eu/digital-agenda/. ( 6 ) Richtlinie 90/385/EWG des Rates (ABl. L 189 vom 20.7.1990, S. 17), Richtlinie 93/42/EWG des Rates (ABl. L 169 vom 12.7.1993, S. 1) und Richtlinie 98/79/EG des Europäischen Parlaments und des Rates (ABl. L 331 vom 7.12.1998, S. 1). http://ec.europa.eu/digital-agenda/ 3. Der beste Weg, eine effektive Rückverfolgbarkeit von Me­ dizinprodukten in der Union zu gewährleisten, ist die Ent­ wicklung eines auf europäischer Ebene harmonisierten UDI- Systems. Die Kommission sollte im Rahmen der laufenden Überarbeitung der geltenden Medizinprodukte-Richtlinien ermächtigt werden, detaillierte Anforderungen an die Rück­ verfolgbarkeit festzulegen. 4. UDI-Mechanismen, die in der Zwischenzeit von den Mit­ gliedstaaten entwickelt werden, müssen miteinander und mit dem künftigen UDI-System der Union kompatibel sein. Dies ist wichtig, um zu vermeiden, dass unterschiedliche, nicht miteinander kompatible Systeme die Ziele des Bin­ nenmarkts untergraben und um die Einführung eines har­ monisierten UDI-Systems der Union zu erleichtern. 5. Diese Empfehlung zielt nicht darauf ab, alle Aspekte des UDI-Systems festzulegen. Sie sollte als Instrument zur Er­ leichterung der Kompatibilität der Rückverfolgbarkeits­ mechanismen auf nationaler und/oder regionaler Ebene die­ nen und der Einführung eines obligatorischen, international kompatiblen UDI-Systems der Union den Weg ebnen. Geltungsbereich der Empfehlung 6. Diese Empfehlung gilt für Medizinprodukte, aktive implan­ tierbare medizinische Geräte (ausgenommen Sonderanferti­ gungen und für klinische Prüfungen bestimmte Produkte) und In-vitro-Diagnostika (ausgenommen in Gesundheitsein­ richtungen hergestellte IVD und IVD für Leistungsbewer­ tungszwecke), einschließlich deren Zubehör. UDI — Entwicklungen auf internationaler Ebene 7. Von der Global Harmonization Task Force (GHTF) ( 1 ) wurde 2008 eine Ad-hoc-Arbeitsgruppe eingesetzt, die ei­ nen international koordinierten Ansatz für UDI entwickeln sollte. 8. Nachdem die GHTF einen Leitfaden ( 2 ) für ein „System für eine einmalige Produktkennzeichnung (UDI) für Medizin­ produkte“ verabschiedet hatte, stellte diese Gruppe, in der die Industrie und die Aufsichtsbehörden vertreten waren und deren Vorsitz die Europäische Kommission führte, ihre Tätigkeit im September 2011 ein. 9. Die Arbeit der GHTF zur weiteren Harmonisierung des Rechtsrahmens für Medizinprodukte findet unter der Schirmherrschaft des Internationalen Forums der Aufsichts­ behörden für Medizinprodukte (dem „International Medical Device Regulators Forum“ — IMDRF) ( 3 ) statt. 10. Diese Empfehlung richtet sich an dem auf internationaler Ebene verfolgten Ansatz aus. UDI — Entwicklungen auf europäischer Ebene 11. Im Jahr 2010 setzte die Europäische Kommission im Rah­ men der Richtlinien über Medizinprodukte eine europäische Ad-hoc-Arbeitsgruppe zu UDI ein, die unter Berücksichti­ gung der Fortschritte auf nationaler und internationaler Ebene einen koordinierten Ansatz entwickeln sollte. 12. Die Gruppe verfolgt drei Ziele: a) Erstens sollen Beiträge der zuständigen Behörden zu den Tätigkeiten auf internationaler Ebene gefördert und ihre Reaktionen auf diese Tätigkeiten beobachtet werden; b) zweitens sollen der Meinungs- und Informationsaus­ tausch in Bezug auf von den Mitgliedstaaten entwickelte nationale Initiativen und die Suche nach gemeinsamen Lösungen gefördert werden; c) drittens soll die Übereinstimmung nationaler Initiativen der Mitgliedstaaten mit den künftigen Unionsvorschrif­ ten erleichtert werden. 2. BEGRÜNDUNG 13. Die Hauptziele eines UDI-Systems sind die Verbesserung der Sicherheit der Patienten ( 4 ) und die Optimierung ihrer Versorgung. Diese Ziele sollen erreicht werden durch a) eine bessere Berichterstattung über Zwischenfälle, b) effizientere Rückrufe und andere Sicherheitskorrektur­ maßnahmen im Feld (Field Safety Corrective Actions — FSCA), c) effizientere Maßnahmen der zuständigen nationalen Be­ hörden nach dem Inverkehrbringen, d) das Ermöglichen einer Datenabfrage in zahlreichen Sys­ temen, e) eine Verringerung der Wahrscheinlichkeit medizinischer Fehler aufgrund einer Fehlanwendung des Produkts. DE L 99/18 Amtsblatt der Europäischen Union 9.4.2013 ( 1 ) Die „Global Harmonization Task Force“ (GHTF) ist ein freiwilliger internationaler Zusammenschluss aus Vertretern der für Medizinpro­ dukte zuständigen Regulierungsbehörden und Berufsverbänden aus Europa, den Vereinigten Staaten von Amerika (USA), Kanada, Japan und Australien. Die GHTF wurde im Jahr 1992 in dem Bemühen gegründet, dem wachsenden Bedarf an internationaler Harmonisie­ rung bei der Regulierung von Medizinprodukten Rechnung zu tra­ gen. Das Mandat der GHTF endete im Dezember 2012. ( 2 ) www.imdrf.org/docs/ghtf/final/steering-committee/technical-docs/ ghtf-sc-n2r3-2011-unique-device-identification-system-110916.pdf ( 3 ) Das Internationale Forum der Aufsichtsbehörden für Medizinpro­ dukte („International Medical Device Regulators Forum“ — IMDRF) wurde im Februar 2011 als Forum für Gespräche über das künftige Vorgehen bei der Harmonisierung der Regulierungsvorschriften für Medizinprodukte gegründet. Es handelt sich um eine Freiwilligen­ gruppe aus Vertretern der für Medizinprodukte zuständigen Regulie­ rungsbehörden aus Australien, Brasilien, Kanada, China (Beobachter), der Europäischen Union, Japan, Russland (Beobachter) und den Ver­ einigten Staaten, die sich zusammengeschlossen haben, um auf der grundlegenden Arbeit der „Global Harmonization Task Force“ (GHTF) aufzubauen. Die Weltgesundheitsorganisation WHO nimmt als Beobachter am IMDRF teil. ( 4 ) Patientensicherheit bedeutet die Verhütung, Vorbeugung und Ab­ schwächung der negative Folgen einer Leistung der Gesundheitsver­ sorgung oder dadurch hervorgerufener Verletzungen. Zu diesen Er­ eignissen zählen „Fehler“, „Abweichungen“ und „Unfälle“. Die Sicher­ heit ergibt sich aus der Wechselwirkung zwischen den verschiedenen Komponenten des Systems; sie hängt nicht von einer Person, einem Produkt oder einer Dienststelle ab. Die Sicherheit kann nur verbes­ sert werden, indem man sich darüber klar wird, wie sie sich aus den Wechselwirkungen zwischen den Komponenten ergibt. Die Patien­ tensicherheit ist ein Teil der Qualität der Gesundheitsversorgung. http://www.imdrf.org/docs/ghtf/final/steering-committee/technical-docs/ghtf-sc-n2r3-2011-unique-device-identification-system-110916.pdf http://www.imdrf.org/docs/ghtf/final/steering-committee/technical-docs/ghtf-sc-n2r3-2011-unique-device-identification-system-110916.pdf 14. Die Einrichtung eines UDI-Systems könnte auch zum Errei­ chen anderer Ziele beitragen, beispielsweise zur Bekämp­ fung von Fälschungen, zur Verbesserung der Vertriebskon­ trolle oder zu Verbesserungen im Bereich der Lagerverwal­ tung und Kostenerstattung. 15. Die in Absatz 14 genannten Ziele sind jedoch als mögliche positive Auswirkungen des UDI-Systems zu betrachten. Verbesserung der Berichterstattung über Zwischenfälle 16. Die Verwendung einer UDI wird voraussichtlich die Bericht­ erstattung bei Zwischenfällen verbessern und bietet die Möglichkeit, alle Zwischenfälle im Zusammenhang mit ei­ nem Medizinprodukt auf Unionsebene, sowie, falls es sich um eine international kompatible und anerkannte UDI han­ delt, auf internationaler Ebene zu erfassen. Damit können die Ergebnisse für die einzelnen Medizinprodukte besser verglichen werden. Effizientere Rückrufe und andere Sicherheitskorrekturmaßnahmen im Feld 17. Die Zuteilung eines einmaligen Kennzeichens für ein be­ stimmtes Medizinprodukt und dessen (weltweite) Verwen­ dung über die gesamte Vertriebskette hinweg ermöglicht die eindeutige Identifizierung des Medizinprodukts. 18. Der von jedem Hersteller entwickelte eigene Rückverfolg­ barkeitsmechanismus reicht nicht aus, um die Rückverfolg­ barkeit zu gewährleisten. Das Fehlen eines unionsweiten Systems über die gesamten Lieferkette hinweg könnte ne­ gative Folgen nach sich ziehen, da jeder an der Vertriebs­ kette beteiligte Akteur die vom Hersteller entwickelte Kenn­ zeichnung verändern könnte. Dies könnte zu Fehlern bei der Codierung von Medizinprodukten führen, was wie­ derum die Rückverfolgbarkeit im Fall von FSCA gefährden würde. Durch die Verwendung einer gleichen Codierungsart wird die Verfolgung und Ortung von Medizinprodukten verbessert. Effiziente Maßnahmen der zuständigen nationalen Behörden nach dem Inverkehrbringen 19. Mit einem UDI-System kann ganz gezielt auf genau be­ stimmte Produkte abgestellt werden. 20. Daneben eröffnet es die Möglichkeit, eine Koordinierung der Reaktionen der Mitgliedstaaten sicherzustellen. Datenabfrage in zahlreichen Systemen 21. Bei Verwendung der gleichen UDI in verschiedenen Daten­ systemen (sowohl bei den Aufsichtsbehörden als auch bei den Gesundheitseinrichtungen) können Daten effizienter abgefragt werden, und die Suche zum Zweck der Erstellung aggregierter Daten wird erleichtert. Derzeit ist ein solcher Ansatz nicht möglich, da jedes Datensystem über sein ei­ genes Identifizierungsinstrument verfügt. Verringerung der Zahl medizinischer Fehler 22. Es ist zu erwarten, dass durch die Nutzung eines Identifi­ zierungsmechanismus die Zahl der Fälle, in denen Medizin­ produkte falsch ausgewählt werden, verringert wird. 3. DEFINITIONEN Im Sinne dieser Empfehlung bezeichnet der Begriff a) ‚Medizinprodukt‘ alle einzeln oder miteinander verbun­ den verwendeten Instrumente, Apparate, Vorrichtungen, Software, Stoffe oder anderen Gegenstände, einschließ­ lich der vom Hersteller speziell zur Anwendung für diagnostische und/oder therapeutische Zwecke bestimm­ ten und für ein einwandfreies Funktionieren des Medi­ zinprodukts eingesetzten Software, die vom Hersteller zur Anwendung für Menschen für folgende Zwecke be­ stimmt sind: — Erkennung, Verhütung, Überwachung, Behandlung oder Linderung von Krankheiten, — Erkennung, Überwachung, Behandlung, Linderung oder Kompensierung von Verletzungen oder Behin­ derungen, — Untersuchung, Ersatz oder Veränderung der Ana­ tomie oder eines physiologischen Vorgangs, — Empfängnisregelung, und deren bestimmungsgemäße Hauptwirkung im oder am menschlichen Körper weder durch pharmakologi­ sche oder immunologische Mittel noch metabolisch er­ reicht wird, deren Wirkungsweise aber durch solche Mit­ tel unterstützt werden kann ( 1 ); b) ‚Aktives implantierbares medizinisches Gerät‘ jedes ak­ tive medizinische Gerät, das dafür ausgelegt ist, ganz oder teilweise durch einen chirurgischen oder medizi­ nischen Eingriff in den menschlichen Körper oder durch einen medizinischen Eingriff in eine natürliche Körp­ eröffnung eingeführt zu werden und dazu bestimmt ist, nach dem Eingriff dort zu verbleiben ( 2 ); c) ‚In-vitro-Diagnostikum‘ jedes Medizinprodukt, das als Reagenz, Reagenzprodukt, Kalibriermaterial, Kontroll­ material, Kit, Instrument, Apparat, Gerät oder System — einzeln oder in Verbindung miteinander — nach der vom Hersteller festgelegten Zweckbestimmung zur In-vitro-Untersuchung von aus dem menschlichen Kör­ per stammenden Proben, einschließlich Blut- und Gewe­ bespenden, verwendet wird und ausschließlich oder hauptsächlich dazu dient, Informationen zu liefern — über physiologische oder pathologische Zustände oder — über angeborene Anomalien oder — zur Prüfung auf Unbedenklichkeit und Verträglich­ keit bei den potenziellen Empfängern oder — zur Überwachung therapeutischer Maßnahmen. DE 9.4.2013 Amtsblatt der Europäischen Union L 99/19 ( 1 ) Artikel 1 Absatz 2 Buchstabe a der Richtlinie 93/42/EWG. ( 2 ) Artikel 1 Absatz 2 Buchstabe c der Richtlinie 90/385/EWG. Probenbehältnisse gelten als In-vitro-Diagnostika. ‚Pro­ benbehältnisse‘ sind luftleere wie auch sonstige Medizin­ produkte, die von ihrem Hersteller speziell dafür gefer­ tigt werden, aus dem menschlichen Körper stammende Proben unmittelbar nach ihrer Entnahme aufzunehmen und im Hinblick auf eine In-vitro-Diagnose aufzubewah­ ren. Erzeugnisse für den allgemeinen Laborbedarf gelten nicht als In-Vitro-Diagnostika, es sei denn, sie sind auf­ grund ihrer Merkmale nach ihrer vom Hersteller fest­ gelegten Zweckbestimmung speziell für In-vitro-Unter­ suchungen zu verwenden ( 1 ); d) ‚Rückverfolgbarkeit‘ die Möglichkeit, die vorangegangene Entwicklung, die Anwendung oder den Aufbewahrungs­ ort des jeweiligen Objekts zu bestimmen; e) ‚Einmalige Produktkennzeichnung‘ (Unique Device Iden­ tification — UDI) eine Abfolge numerischer oder alpha­ numerischer Zeichen, die mittels eines international an­ erkannten Identifizierungs- und Codierungsstandards er­ stellt wurde, und die eine eindeutige Identifizierung ein­ zelner Medizinprodukte auf dem Markt ermöglicht. Die UDI besteht aus der Produktkennung (Device Identifier) und der Herstellungskennung (Production Identifier); f) ‚Produktkennung‘ eine einmalige Abfolge numerischer oder alphanumerischer Zeichen, die einem bestimmten Hersteller und Produkt eigen ist; g) ‚Herstellungskennung‘ eine einmalige Abfolge numeri­ scher oder alphanumerischer Zeichen, die Angaben im Zusammenhang mit der Produktionseinheit des Pro­ dukts enthält; h) ‚UDI-Träger‘ die Form, in der die einmalige Produkt­ kennzeichnung durch die automatische Identifikation und Datenerfassung (Automatic Identification and Data Capture ( 2 ) — AIDC) wiedergegeben wird und gegebe­ nenfalls die vom Menschen lesbare Form (Human Rea­ dable Interpretation — HRI). i) ‚Elektronisches UDI-System‘ einen zentralen Datenspei­ cher/eine zentrale Datenbank, in der Identifikationscodes und damit zusammenhängende/dazugehörige Identifika­ tionsdaten für bestimmte auf dem Unionsmarkt in Ver­ kehr gebrachte Produkte gespeichert werden; j) ‚Vom Menschen lesbare Form‘ ein Format, in dem AIDC-Daten vom Menschen gelesen werden können; k) ‚Direktmarkierung‘ alle Technologien, mit denen ein Symbol auf der Oberfläche eines Gegenstands (z. B. durch Herstellen zweier unterschiedlicher Oberflächen­ beschaffenheiten durch Lasergravur, das Einprägen oder -hämmern von Symbolen oder durch andere Technolo­ gien wie Tintenstrahl-Beschriftung oder Flexodruck) an­ gebracht wird; l) ‚Hersteller‘ die natürliche oder juristische Person, die für die Gestaltung, Herstellung, Verpackung und Etikettie­ rung eines Produkts im Hinblick auf das Inverkehrbrin­ gen im eigenen Namen verantwortlich ist, unabhängig davon, ob diese Tätigkeiten von dieser Person oder stell­ vertretend für diese von einer dritten Person ausgeführt werden ( 3 ); m) ‚Bevollmächtigter Vertreter‘ eine in der Union nieder­ gelassene natürliche oder juristische Person, die vom Hersteller ausdrücklich dazu bestimmt wurde, im Hin­ blick auf seine Verpflichtungen nach den einschlägigen Rechtsvorschriften der Gemeinschaft in seinem Namen zu handeln und von den Behörden und Stellen in der Gemeinschaft in diesem Sinne kontaktiert zu werden ( 4 ); n) ‚Importeur‘ eine in der Union niedergelassene natürliche oder juristische Person, die ein Produkt aus einem Dritt­ land auf dem Unionsmarkt in Verkehr bringt ( 5 ); o) ‚Händler‘ eine natürliche oder juristische Person in der Lieferkette, die ein Produkt auf dem Markt bereitstellt, mit Ausnahme des Herstellers oder des Importeurs ( 6 ); p) ‚Wirtschaftsakteure‘ den Hersteller, den bevollmächtigten Vertreter, den Importeur und den Händler ( 7 ); q) ‚Gesundheitseinrichtung‘ eine Organisation, deren Hauptzweck in der Versorgung oder Behandlung von Patienten und/oder der Förderung der öffentlichen Ge­ sundheit besteht; r) ‚Anwender‘ einen Angehörigen der Gesundheitsberufe oder Laien, der ein Medizinprodukt verwendet. 4. RISIKOBASIERTER ANSATZ 23. Mitgliedstaaten, die vorhaben, ein UDI-System einzurichten, sollten einem der Klassifizierung des Produkts angemesse­ nen risikobasierten Ansatz folgen. 24. Das UDI-System sollten stufenweise eingeführt werden, be­ ginnend mit den Produkten der höchsten Risikoklasse, für die die Bedingungen für das Anbringen der UDI zuerst gelten sollten. UDI-Typ 25. Die UDI sollte aus zwei Teilen bestehen, einer Produktken­ nung und einer Herstellungskennung. DE L 99/20 Amtsblatt der Europäischen Union 9.4.2013 ( 1 ) Artikel 1 Absatz 2 Buchstabe b der Richtlinie 98/79/EG. ( 2 ) Die automatische Identifizierung und Datenerfassung bezieht sich auf Verfahren zur automatischen Identifizierung von Objekten, zur Erhebung von Daten über diese und die automatische Eingabe der betreffenden Daten in Computersysteme. ( 3 ) Artikel 1 Absatz 2 Buchstabe f der Richtlinie 93/42/EWG. ( 4 ) Artikel 1 Absatz 2 Buchstabe j der Richtlinie 93/42/EWG. ( 5 ) Artikel 2 Absatz 5 der Verordnung (EG) Nr. 765/2008 des Europäi­ schen Parlaments und des Rates (ABl. L 218 13.8.2008, S. 30). ( 6 ) Artikel 2 Absatz 6 der Verordnung (EG) Nr. 765/2008. ( 7 ) Artikel 2 Absatz 7 der Verordnung (EG) Nr. 765/2008. 26. Die Produktkennung sollte statische Informationen ( 1 ) zu Hersteller und Produktmodell enthalten und dient auch als „Zugangsschlüssel“ zu Informationen in einer UDI-Da­ tenbank. 27. Die Herstellungskennung sollte variable Informationen ( 2 ) enthalten, aus denen Daten in Bezug auf die Produktions­ einheit sowie das erreichte Niveau der Rückverfolgbarkeit hervorgehen. 28. Die UDI sollte sowohl in einer von Menschen lesbaren Form (die aus einer vom Menschen lesbaren Abfolge nu­ merischer oder alphanumerischer Zeichen besteht) als auch in einer mittels einer AIDC-Technologie lesbaren und mit­ tels eines Datenträgers übermittelbaren Form erscheinen. 29. Gibt es erhebliche Probleme, beide Formate — AIDC und HRI — auf dem Etikett unterzubringen, sollte das AIDC- Format bevorzugt werden. Allerdings könnte in bestimmten Umgebungen oder Situationen, wie in der häuslichen Pfle­ ge, die Verwendung von HRI gegenüber AIDC zu bevor­ zugen sein. 30. Die Mitgliedstaaten sollten überwachen, dass die Unter­ scheidung zwischen den verschiedenen Klassen von Produk­ ten gemäß Absatz 31 ausschließlich auf der Grundlage der Herstellungskennung (also der variablen Informationen) er­ folgt. 31. Allgemein gilt, dass die Herstellungskennung je nach Risi­ koklasse des Produkts unterschiedliche Daten (variable In­ formationen) enthalten muss ( 3 ): — Verfallsdatum und/oder Herstellungsdatum bei Produk­ ten der Risikoklasse I — Chargen-/Partienummer bei Produkten der Risikoklasse IIa, — Chargen-/Partienummer bei Produkten der Risikoklasse IIb, — Chargen-/Partienummer oder Seriennummer ( 4 ) bei Pro­ dukten der Risikoklasse III. 32. Den Herstellern steht es frei, gegebenenfalls eine Herstel­ lungskennung (variable Informationen) zu verwenden, die für eine höhere Risikoklasse als die des betreffenden Pro­ duktes vorgesehen ist. Anbringung der UDI 33. Allgemein sollte UDI auf jeder Verpackungsebene aller Pro­ duktklassen angebracht werden ( 5 ). 34. Der UDI-Träger (AIDC- und HRI-Darstellung der UDI) sollte sich auf dem Etikett des Produkts, seiner Verpackung oder auf dem Produkt selbst (Direktmarkierung) sowie auf allen höheren Ebenen der Verpackung ( 6 ) befinden. 5. VON DEN WIRTSCHAFTSAKTEUREN, GESUNDHEITS­ EINRICHTUNGEN UND BERUFSMÄSSIGEN ANWENDERN ZU ERFÜLLENDE VORAUSSETZUNGEN 35. Um die Ziele des UDI-Systems zu erreichen, sollten die Wirtschaftsakteure und die Gesundheitseinrichtungen bei der Entwicklung ihrer eigenen nationalen UDI-Mechanis­ men über die gesamte Lieferkette hinweg Informationen zur Produktkennung (statische Informationen) und zur Her­ stellungskennung (variable Informationen) speichern. Ge­ sundheitseinrichtungen und, soweit möglich, berufsmäßige Anwender sollten diese Informationen bei der Berichterstat­ tung über Zwischenfälle benutzen. Dies ermöglicht ins­ besondere effizientere Maßnahmen beim Rückruf oder bei der Rücknahme von Produkten. 36. Informationen im Zusammenhang mit der Produktkennung (statische Informationen) sollten in den nationalen UDI-Da­ tenbanken erfasst werden. 37. Sobald die künftige Europäische Datenbank für Medizinpro­ dukte (EUDAMED) eingerichtet ist, werden die Informatio­ nen im Zusammenhang mit der Produktkennung (statische Informationen) auf europäischer Ebene in einem elektro­ nischen UDI-System zusammengefasst, das Teil von EUDA­ MED ist. 38. Die Informationen im Zusammenhang mit der Herstel­ lungskennung (variable Informationen) sollten nicht an die nationalen UDI-Datenbanken geschickt werden und werden nicht in das europäische elektronische UDI-System aufgenommen. Für die Zwecke dieser Empfehlung sollten die Wirtschafts­ akteure, Gesundheitseinrichtungen und berufsmäßigen An­ wender folgende Anforderungen erfüllen: Hersteller 39. Erstens sollten die Hersteller den von ihnen hergestellten Medizinprodukten eine geeignete UDI (statischer und varia­ bler Teil) zuteilen. 40. Zweitens sollten sie die erforderlichen Datenelemente (siehe Anhang) zur Eingabe in die UDI-Datenbank weiterleiten. DE 9.4.2013 Amtsblatt der Europäischen Union L 99/21 ( 1 ) Diese Informationen sind für alle Produkte desselben spezifischen Modells gleich. ( 2 ) Diese Informationen unterscheiden sich je nach Art der Kontrolle des Herstellungsprozesses (Verfallsdatum oder Herstellungsdatum, Los- oder Chargennummer, Seriennummer). ( 3 ) Mögliche Ausnahmen und/oder Freistellungen von der allgemeinen Regel sollten je nach Risikoklasse im Einklang mit den internationa­ len Leitlinien berücksichtigt werden. ( 4 ) Die Seriennummer ermöglicht die Identifizierung der einzelnen Pro­ dukteinheit. ( 5 ) Mögliche Ausnahmen und/oder Freistellungen von der allgemeinen Regel sollten je nach Risikoklasse im Einklang mit den internationa­ len Leitlinien berücksichtigt werden. ( 6 ) Gemäß internationalen Leitlinien fallen Paletten nicht unter den Be­ griff der höheren Ebenen der Verpackung, daher gelten die UDI- Bedingungen nicht für Paletten. 41. Drittens sollte sie die Etikettierung ihrer Produkte ändern, um den UDI-Code, soweit dies praktisch möglich ist, auf dem Etikett des Produkts, seiner Verpackung oder auf dem Produkt selbst (Direktmarkierung) sowie auf allen höheren Ebenen der Verpackung gemäß Absatz 34 anzubringen. 42. Viertens sollten sie elektronische Aufzeichnungen sowohl über die Produktkennung (statische Informationen) als auch über die Herstellungskennung (variable Informationen) führen. 43. Schließlich sollten sie ein elektronisches Verzeichnis der Wirtschaftsakteure, Gesundheitseinrichtungen oder berufs­ mäßigen Anwender führen, an die sie jedes einzelne Pro­ dukt geliefert haben. Importeure 44. Erstens sollten die Importeure sicherstellen, dass der Her­ steller dem Produkt eine geeignete UDI (statischer und va­ riabler Teil) zugeteilt hat, bevor sie es in der Union in Verkehr bringen. Ist ein Importeur der Auffassung oder hat er Grund zu der Annahme, dass diese Bedingung nicht erfüllt ist, sollte er das betreffende Produkt nicht in der Union in Verkehr bringen, bis es mit den Vorschriften in Einklang gebracht wird. 45. Zweitens sollten die Importeure die UDI weder entfernen noch verändern, da andernfalls keine Rückverfolgbarkeit möglich ist. 46. Drittens sollten sie sich vergewissern, dass das Produkt be­ reits in der UDI-Datenbank des Mitgliedstaats, in dem es in der Union in Verkehr gebracht wurde, registriert ist. 47. Wurde das Produkt bereits registriert, sollten sie überprü­ fen, ob die Produktkennung (statische Informationen) auf dem Produkt der in der UDI-Datenbank eingetragenen ent­ spricht. 48. Wurde das Produkt noch nicht registriert, sollten die Im­ porteure sich an die Anforderungen an die Registrierung der Informationen im Zusammenhang mit der Produktken­ nung (statische Informationen) halten. 49. Viertens sollten sie elektronische Aufzeichnungen sowohl über die Produktkennung (statische Informationen) als auch über die Herstellungskennung (variable Informationen) führen. 50. Fünftens sollten sie ein elektronisches Verzeichnis der Wirt­ schaftsakteure führen, von denen sie ein Produkt bezogen haben. 51. Schließlich sollten sie ein elektronisches Verzeichnis der Wirtschaftsakteure, Gesundheitseinrichtungen oder berufs­ mäßigen Anwender führen, an die sie das Produkt geliefert haben. Bevollmächtigte Vertreter 52. Hat ein Hersteller, der im eigenen Namen ein Produkt in Verkehr bringt, keine eingetragene Niederlassung in einem Mitgliedstaat, so benennt er einen einzigen bevollmächtig­ ten Vertreter in der Union. Die Benennung des bevollmäch­ tigten Vertreters muss mindestens für alle Medizinprodukte desselben Modells gelten. 53. Die bevollmächtigten Vertreter sollten auf Verlangen Zu­ gang zu den Aufzeichnungen sowohl über die Produktken­ nung (statische Informationen) als auch über die Herstel­ lungskennung (variable Informationen) für die betreffenden Produkte haben, für die sie benannt sind. Händler 54. Erstens sollten die Händler, bevor sie ein Produkt auf dem Markt bereitstellen, überprüfen, dass der Hersteller bzw. gegebenenfalls der Importeur dem Produkt eine geeignete UDI (statischer und variabler Teil) zugeteilt hat. Ist ein Händler der Auffassung oder hat er Grund zu der Annah­ me, dass diese Bedingung nicht erfüllt ist, sollte er das betreffende Produkt nicht auf dem Unionsmarkt bereitstel­ len, bis es mit den Vorschriften in Einklang gebracht wird. 55. Zweitens sollten die Händler die UDI weder entfernen noch verändern, da andernfalls keine Rückverfolgbarkeit möglich ist. 56. Drittens sollten sie elektronische Aufzeichnungen sowohl über die Produktkennung (statische Informationen) als auch über die Herstellungskennung (variable Informationen) führen. 57. Viertens sollten sie ein elektronisches Verzeichnis der Wirt­ schaftsakteure führen, von denen sie ein Produkt bezogen haben. 58. Schließlich sollten sie ein elektronisches Verzeichnis der Wirtschaftsakteure, Gesundheitseinrichtungen oder berufs­ mäßigen Anwender führen, an die sie ein Produkt geliefert haben. Gesundheitseinrichtungen 59. Erstens sollten Gesundheitseinrichtungen elektronische Auf­ zeichnungen sowohl über die Produktkennung (statische Informationen) als auch über die Herstellungskennung (va­ riable Informationen) der Produkte führen, die bei ihnen eingehen. Für die Berichterstattung über Zwischenfälle soll­ ten Gesundheitseinrichtungen sowohl die Informationen der Produktkennung (statische Informationen) als auch die der Herstellungskennung (variable Informationen) über das Produkt, bei dem ein Zwischenfall aufgetreten ist, verwen­ den. 60. Zweitens sollte für bestimmte Produkte, beispielsweise sol­ che, die für Verfahren mit hohem Risiko eingesetzt werden und/oder die für besonders gefährdete Patienten bestimmt sind, eine Verbindung zwischen dem verwendeten Produkt und dem damit behandelten Patienten hergestellt werden. Gesundheitseinrichtungen sollten daher Aufzeichnungen darüber führen, welches Produkt bei welchem Patienten verwendet wurde. DE L 99/22 Amtsblatt der Europäischen Union 9.4.2013 61. Drittens sollten Gesundheitseinrichtungen für bestimmte Produkte wie implantierbare medizinische Geräte sowohl die Produktkennung als auch die Herstellungskennung in der elektronischen Patientenakte speichern. Im Fall einer Rückrufaktion sollte genau festzustellen sein, welches Me­ dizinprodukt welchem Patienten implantiert wurde. Berufsmäßige Anwender 62. Soweit möglich sollten berufsmäßige Anwender für die Be­ richterstattung über Zwischenfälle sowohl die Informatio­ nen der Produktkennung (statische Informationen) als auch die der Herstellungskennung (variable Informationen) über das Produkt, bei dem ein Zwischenfall aufgetreten ist, ver­ wenden. 6. NATIONALE UDI- DATENBANKEN Datenelemente 63. Mitgliedstaaten, die ein UDI-System für Medizinprodukte einzurichten beabsichtigen, werden gebeten, dabei auf na­ tionalen UDI-Datenbanken aufzubauen. 64. Die Mitgliedstaaten werden ersucht, für die Zwecke dieser Empfehlung die Verwendung der erweiterbaren Auszeich­ nungssprache XML (Extensible Markup Language) als ge­ meinsames Format für den Datenaustausch zwischen den UDI-Datenbanken zu bevorzugen und die einschlägigen Spezifikationen und semantischen Normen in diesem Be­ reich zu berücksichtigen. 65. Im Anhang sind die Datenelemente aufgeführt, die in die nationalen UDI-Datenbanken eingegeben werden und die den Elementen der Produktkennung (statische Informatio­ nen) entsprechen sollten. Brüssel, den 5. April 2013 Für die Kommission Tonio BORG Mitglied der Kommission DE 9.4.2013 Amtsblatt der Europäischen Union L 99/23 ANHANG DATENELEMENTE DER NATIONALEN UDI-DATENBANKEN Die nationalen UDI-Datenbanken sollten folgende Datenelemente enthalten: a) Menge pro Packung, b) gegebenenfalls alternative oder zusätzliche Kennung(en), c) wie die Herstellung des Produkts kontrolliert wird (Verfallsdatum oder Herstellungsdatum, Los- oder Chargennummer, Seriennummer), d) gegebenenfalls die Produktkennung der Gebrauchseinheit (falls für das Produkt auf der Ebene der Gebrauchseinheit keine UDI vergeben wurde, sollte eine „Gebrauchseinheitskennung“ zugeteilt werden, um die Verwendung eines Produkts einem Patienten zuzuordnen), e) Name und Anschrift des Herstellers (wie auf dem Etikett angegeben), f) gegebenenfalls Name und Anschrift des bevollmächtigten Vertreters (wie auf dem Etikett angegeben), g) Code der Globalen Nomenklatur für Medizinprodukte (GMDN) oder international anerkannter Nomenklatur-Code, h) gegebenenfalls Handels-/Markenname, i) gegebenenfalls Modell-, Referenz- oder Katalognummer des Produkts, j) gegebenenfalls klinische Größe (einschließlich Volumen, Länge, Breite, Durchmesser), k) zusätzliche Produktbeschreibung (fakultativ), l) gegebenenfalls Lagerungs- und/oder Handhabungshinweise (wie auf dem Etikett oder in der Gebrauchsanweisung angegeben), m) gegebenenfalls zusätzliche Handelsnamen des Produkts, n) als Produkt zum Einmalgebrauch ausgewiesen (j/n), o) gegebenenfalls beschränkte Anzahl der Wiederverwendungen, p) Produkt steril verpackt (j/n), q) Sterilisation vor Verwendung erforderlich (j/n), r) als Latex enthaltendes Produkt ausgewiesen (j/n), s) als DEPH enthaltendes Produkt ausgewiesen (j/n), t) URL-Adresse für zusätzliche Informationen, z. B. elektronische Gebrauchsanweisung (fakultativ), u) gegebenenfalls wichtige Warnhinweise oder Kontraindikationen. DE L 99/24 Amtsblatt der Europäischen Union 9.4.2013 Empfehlung der Kommission vom 5. April 2013 über einen gemeinsamen Rahmen für ein System einmaliger Produktkennzeichnung für Medizinprodukte in der Union (Text von Bedeutung für den EWR) (2013/172/EU)

Title: Authoring Group: Date: IMDRF IMDRF/WG/N7FINAL:2013 International Medical Device Regulators Forum Final Document UDI Guidance Unique Device Identification (UDI) of Medical Devices IMDRF UDI Working Group 9 December 2013 RF Chair This document was produced by the International Medical Device Regulators Forum. There are no restrictions on the reproduction or use of this document; however, incorporation of this document, in part or in whole, into another document, or its translation into languages other than English, does not convey or represent an endorsement of any kind by the International Medical Device Regulators Forum. Copyright© 2013 by the International Medical Device Regulators Forum. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 2 of 19 Contents 1. Preamble ..................................................................................................................................... 3 2. Introduction ................................................................................................................................. 3 2.1 Traceability 4 2.2 Identification 4 2.3 Adverse Event Reporting and Field Safety Corrective Actions 4 2.4 Medical errors 5 2.5 Documentation 5 2.6 Other considerations 5 3. Rationale, purpose and scope ...................................................................................................... 5 3.1 Rationale 5 3.2 Purpose 5 3.3 Scope 6 4. References ................................................................................................................................... 6 5. Definitions................................................................................................................................... 7 6. Guidance for a UDI System ........................................................................................................ 9 7. The UDI .................................................................................................................................... 10 8. UDI Carrier ............................................................................................................................... 11 9. The UDI Database (UDID) ....................................................................................................... 13 9.1 General principles of the UDID 13 9.2 The core UDID data elements 13 10. Rules for specific device types ............................................................................................... 15 10.1 Implantable devices 15 10.2 Reusable devices requiring reprocessing between uses 15 10.3 Non IVD kits 15 10.4 IVD Kits 16 10.5 Configurable medical device systems 16 10.6 Software as a Medical Device (SaMD) 17 10.6.1. UDI Assignment Criteria 17 10.6.2 UDI Placement Criteria 17 11. Annex ..................................................................................................................................... 19 IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 3 of 19 1. Preamble This document is inscribed in the framework of the International Medical Device Regulators Forum (IMDRF). It replaces the "Guidance on a Unique Device Identification (UDI) System for Medical Devices" adopted by the Global Harmonization Task Force (GHTF) on 16 September 2011. The IMDRF Guidance on a "Unique Device Identification (UDI) System for Medical Devices" clarifies and supplements the above mentioned GHTF Guidance by providing non-binding rules for use in the regulation of medical devices, and has been subject to consultation throughout its development. There are no restrictions on the reproduction, distribution or use of this document; however, incorporation of this document, in part or in whole, into any other document, or its translation into languages other than English, does not convey or represent an endorsement of any kind by the IMDRF. 2. Introduction This guidance provides a framework for those regulatory authorities that intend to develop their UDI Systems that achieves a globally harmonized approach to the UDI. The framework can be used at a local, national, or global level such that these systems are implemented without regional or national differences. This guidance is intended to provide a high-level conceptual view of how a global UDI System should work. It is recognized that further additional guidance may be needed once these core concepts are accepted. The fundamental concepts of a globally harmonized UDI System include: a. the UDI and UDI Carrier are based on standards, b. a UDI applied to a medical device anywhere in the world should be able to be used globally and to meet the UDI requirements of its regulatory authority, c. national or local identification numbers should NOT be a substitute for UDI, d. regulatory authorities should not specify the procedure for modifying these UDI standards e. the UDID core elements should not be modified, f. the UDID should use the Health Level Seven International (HL7) Structured Product Label (SPL) and web based interface for data submission, g. every medical device needs to be identified by a UDI, unless it is exempted The UDI System is intended to provide a single, globally harmonized system for positive identification of medical devices. Healthcare professionals and patients will no longer have to access multiple, inconsistent, and incomplete sources in an attempt to identify a medical device and, its key attributes. The UDID is a designated source for additional information. It is critical to note that the benefits of UDI can only accrue if all stakeholders, from the manufacturer to healthcare providers and patients, use UDI throughout their workflow systems. Therefore, it is imperative that all stakeholders be educated about the development and use of a UDI System. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 4 of 19 A globally harmonized and consistent approach to UDI is expected to increase patient safety and help optimize patient care by facilitating the: a. traceability of medical devices, especially for field safety corrective actions, b. adequate identification of medical devices through distribution and use, c. identification of medical devices in adverse events, d. reduction of medical errors, e. documenting and longitudinal capture of data on medical devices. 2.1 Traceability The global use of a UDI will facilitate traceability throughout distribution. In order to achieve traceability, it is necessary to involve all stakeholders to capture and store the UDI (Device Identifier (UDI-DI) + Production Identifier (UDI-PI)) throughout distribution and use. This is especially important for field safety corrective actions. Though the UDID does not capture UDI-PI, it is expected that supply chain operators will capture and use these identifiers. This is critical during field safety corrective actions. In addition, the foundational use of UDI can help fight counterfeiting and secure the supply chain for all stakeholders. Traceability can be facilitated by1: a. recording medical devices from manufacturer to healthcare provider throughout the supply chain, b. recording medical device use in patients, c. implementation of medical device field safety corrective actions, d. a standardized way to input medical device identification into health related registries. 2.2 Identification UDI will facilitate the unambiguous identification of the medical device through distribution and use by providing a single global identifier that can be used to link and integrate existing government, clinical, hospital, and industry databases. UDI should allow for improved procurement, inventory management, and accounting. The existence of a single UDI-DI to link disparate data bases should allow creative new medical and business applications, and synergy among those applications. 2.3 Adverse Event Reporting and Field Safety Corrective Actions UDI will allow industry and regulatory authorities to more rapidly identify medical devices involved in adverse events. UDI will be available for inclusion in adverse event reports, allowing greater accuracy in reporting, and more rapid aggregation of related reports. Using this 1 In the case of medical devices containing medical products of human origin, the traceability chain must, for purposes of vigilance, begin with the donor, and trace the human material through all of its processing steps. For these kind of devices the ISBT 128 system has been developed to ensure a complete traceability chain from donor to patient as required for medical devices containing medical products of human origin. . IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 5 of 19 information, Health Authorities can more rapidly collate and analyze problem reports and identify the most-appropriate solution for a particular concern. UDI will allow more targeted safety alerts and field safety corrective actions on the specific medical devices that are of concern. 2.4 Medical errors By providing rapid and electronic access to critical patient safety information, such as clinical size, sterilization status, etc. related to a medical device, the UDI system may help clinicians more safely select and use the proper medical device for a patient. UDID data could be downloaded by healthcare providers to be used for internal reference of safety related information. 2.5 Documentation The use of UDI System will facilitate and simplify the documentation of medical device use in various patient records including traditional as well as electronic health records and registries. UDI should also enable linkages of medical device information across various systems and across geographies. These applications of UDI could help identifying medical device problems and enhance comparative effectiveness. 2.6 Other considerations Other considerations essential for the successful development and implementation of a globally harmonized UDI System include: a. a risk-based approach which is essential given the huge diversity of the medical devices, b. application to kits, systems and other groups of devices which need to be managed appropriately, c. requirements which should be phased in over a period of years based on risk classes, starting with the highest risk class, to reduce the burden of implementation, d. the need for all supply chain stakeholders to have sufficient time to prepare their systems, processes and staff, for the proper use of the UDI System, e. Effective data retrieval systems. 3. Rationale, purpose and scope 3.1 Rationale There are currently no global definitions of what constitutes a UDI or UDI System. As a consequence, discrepancies between different national approaches do exist and will most likely increase. Common globally harmonized UDI System requirements would offer significant benefits to manufacturers, healthcare providers, patients, and regulatory authorities. In addition, a globally harmonized UDI System will limit the cost of regulatory compliance. 3.2 Purpose IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 6 of 19 This guidance intends to avoid country-specific requirements regarding the core elements of the UDI System by developing common guidance for: a. creating, using and maintaining a UDI, b. applying a UDI Carrier, c. establishing the UDID model/structure, with a defined list of Data Elements, d. establishing basic requirements for a data submission format based on HL7 SPL and web based interface and e. establishing basic requirements for a common data exchange standard. This document does not address the use of the UDI System, e.g. by healthcare providers. Therefore it does not directly address issues associated with counterfeit medical devices or how to enable better control of purchasing which will depend on the use of the UDI System by healthcare providers. 3.3 Scope This document applies to all products to be placed on the market that are regulated as medical devices. For a definition of a medical device, see the GHTF document entitled "Information Document Concerning the Definition of the Term “Medical Device”". This document is addressed to the regulatory authorities and affects medical device manufacturers and other relevant stakeholders. 4. References - GHTF SG1/N071:2012 Definition of the Terms ‘Medical Device’ and ‘In Vitro Diagnostic (IVD) Medical Device’; - GHTF SG1/N070:2011 Label and Instructions for Use for Medical Devices; - GHTF SG1/N055:2009 Definitions of Terms Manufacturer, Authorized Representative, Distributor and Importer; - GHTF SG1/N065:2010 Registration of Manufacturers and other Parties and Listing of Medical Devices; - GHTF SG1/N77:2012 Principles of Medical Devices Classification - GHTF SG1/N044:2008 Role of Standards in the Assessment of Medical Devices - GHTF SG2/N5:2006 Contents of Field Safety Notice - IMDRF SaMD WG/N10/FINAL:2013 Software as a Medical Device (SaMD): Key Definitions; - ISO/IEC 15459-2 – Information technology - Unique identifiers – Part 2: Registration procedures; - ISO/IEC 15459-4:2008 – IT Unique identifiers Part 4: Individual items; - ISO/IEC 15459-6:2007 – IT Unique identifiers Part 6: Unique identifier for product groupings; - ISO/IEC 16022:2006 – Information technology – Automatic identification and data capture techniques – Data Matrix bar code symbology specification; - ISO/IEC 18004:2006 – IT AIDC techniques QR Code 2005 bar code symbology specification; - ISO/IEC 15417:2007 – IT AIDC techniques – Code 128 bar code symbology specification. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 7 of 19 5. Definitions Accessory Accessory means an article intended specifically by its manufacturer to be used together with a specific medical device(s), to enable the medical device to be used in accordance with its intended use [modified draft GHTF definition –GHTF/SG1/N071:2012]. Automatic Identification and Data Capture (AIDC) A technology used to automatically capture data. AIDC technologies include bar codes, smart cards, biometrics and RFID. Configurable medical device system A configurable medical device system consists of several components which can be assembled in multiple configurations. Those individual components may be medical devices itself and/or non- medical devices. Examples are Computed Tomography (CT) systems, Ultrasound systems, Anesthesia systems, Physiological Monitoring systems, Radiology Information System (RIS). Configuration Configuration is a combination of items of equipment, as specified by the manufacturer, that operate together to provide an intended use or purpose as a medical device. The combination of items may be modified, adjusted or customized to meet a customer need. Examples: 1. CT: gantry, tube, table, console are items of equipment that can be configured/combined to deliver an intended function. 2. Anesthesia: ventilator, breathing circuit, vaporizer are items of equipment that can be configured/combine to deliver an intended function. Device Identifier (UDI-DI) The UDI-DI is a unique numeric or alphanumeric code specific to a model of medical device and that is also used as the "access key" to information stored in a UDID. Examples of the UDI-DI include GS1 GTIN (Global Trade Item Number), HIBC-LIC (Labeler Identification Code), ISBT 128-PPIC (Processor Product Identification Code). Human Readable Interpretation (HRI) Human Readable Interpretation is a legible interpretation of the data characters encoded in the UDI Carrier. Implantable device Any device, including those that are partially or wholly absorbed, which is intended: -  to be totally introduced into the human body or,  to replace an epithelial surface or the surface of the eye, by surgical intervention which is intended to remain in place after the procedure. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 8 of 19 Any device intended to be partially introduced into the human body through surgical intervention and intended to remain in place after the procedure for at least 30 days is also considered an implantable device. [GHTF SG1/N77:2012] Kits Kits are a collection of products, including medical devices, that are packaged together to achieve a common intended use and is being distributed as a medical device. These could also be called procedure packs or convenience kits. Note: Jurisdictions may differ in their definition of kit. Label Written, printed, or graphic information either appearing on the medical device itself, or on the packaging of each unit, or on the packaging of multiple devices [GHTF/SG1/N070:2011]. Manufacturer Manufacturer means any natural or legal person 2 with responsibility for design and/or manufacture of a medical device with the intention of making the medical device available for use, under his name; whether or not such a medical device is designed and/or manufactured by that person himself or on his behalf by another person(s) [GHTF SG1/N55:2009]. This includes reprocessors and remanufacturers that take responsibility for the device and reintroduce it into commercial distribution. Own Brand/Private Labelers An Own Brand or Private Labeler relabels a device from a 3rd party with his own name without making any further changes to the device thereby taking responsibility for it as the manufacturer. Packaging Levels Packaging levels means the various levels of device packages that contain a fixed quantity of medical devices, e.g. each, carton, case. Note: This does not include shipping containers. Production Identifier (UDI-PI) The Production Identifier is a numeric or alphanumeric code that identifies the unit of device production. The different types of Production Identifier(s) include serial number, lot/batch number, Software as a Medical Device (SaMD) version and manufacturing and/or expiration date. Radio Frequency Identification (RFID) RFID is a technology that uses communication through the use of radio waves to exchange data between a reader and an electronic tag attached to an object, for the purpose of identification. Shipping containers Shipping container is a container where the traceability is controlled by a process specific to logistics systems. 2 The term “person” that appears here includes legal entities such as a corporation, a partnership or an association. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 9 of 19 Software as a Medical Device (SaMD) The term SaMD is defined as software intended to be used for one or more medical purposes that perform these purposes without being part of a hardware medical device. [IMDRF SaMD WG/ N10R4FINAL:2013] Standard Document, established by consensus and approved by a recognized body, that provides, for common and repeated use, rules, guidelines or characteristics for activities or their results, aimed at the achievement of the optimum degree of order in a given context. [GHTF/SG1/N044:2008] Unit of Use (UoU) UDI-DI The UoU UDI-DI is an identifier assigned to an individual medical device. It is assigned in instances when a UDI is not labelled at the level of the device unit of use (e.g. several units contained in a plastic bag). Its purpose is to associate the use of a device to/on a patient.3 Unique Device Identification The UDI is a series of numeric or alphanumeric characters that is created through a globally accepted device identification and coding standard. It allows the unambiguous identification of a specific medical device on the market. The UDI is comprised of the UDI-DI and UDI-PI. Note: The word "Unique" does not imply serialization of individual production units. UDI System The UDI System is the framework for: 1) UDI production , 2) UDI application on the label or on the device, and 3) UDI Database (UDID) fundamental contents UDI Carrier The UDI Carrier is the means to convey the UDI by using AIDC and, if applicable, its HRI. Note: Carriers can include ID/linear bar code, 2D/Matrix bar code, RFID, etc… UDI Database (UDID) The UDID contains identifying information and other elements associated with the specific medical device. 6. Guidance for a UDI System A UDI System comprises 3 parts: 1. the development of the UDI using globally accepted standards, (see section 7) 2. the application of that UDI on the label, (see section 8) and 3. the submission of appropriate information to a UDID (see section 9). 3 Because of their nature, the Unit of Use is not appropriate to in vitro diagnostic medical devices. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 10 of 19 In order to facilitate a globally harmonized approach to UDI, it is imperative that: 1. the marking of the UDI should be an additional requirement – it does not replace any other marking or labeling requirements. However UDI should replace any existing medical device identifier used in accordance to local regulations with the same purpose of the UDI System; 2. the manufacturer should create and maintain globally unique UDIs on his medical devices; 3. only the manufacturer can establish the UDI on the device or its packaging. Reprocessors of single use medical devices, remanufacturers, relabelers and own brand/private labelers are considered the manufacturer of the reprocessed, remanufactured or relabeled device and, as such, are also subject to these requirements; 4. globally accepted ISO/IEC coding standards implemented by global organizations, such as GS1, HIBCC and ICCBBA, meet the criteria of the UDI and manufacturers shall be permitted to choose which system to use. These organizations have responsibility for maintaining the global uniqueness of their coding systems. It is imperative that these coding systems be adopted and implemented, without national deviations or changes to these global coding systems; proliferation of coding systems must be discouraged; 5. national or regional regulatory requirements shall not restrict methods of AIDC as this will hinder the establishment of a globally harmonized UDI System; 6. the national/regional regulation for UDI System shall include a robust and transparent mechanism for evaluating and adjudicating requests for UDI exemptions in alternative placements of UDI-DI and UDI-PI. Such exemptions should cover all the products with the same characteristics; 7. the regulators of the UDI System shall specify harmonized exemptions for certain devices such as investigational devices and custom made devices from UDI requirements; 8. common criteria for recognition are: a. The employed UDI must meet the requirements of the globally harmonized UDI System to adequately identify a device through its distribution, b. The employed UDI is in compliance with globally accepted standards ISO/IEC 15459-2, ISO/IEC 15459-4 and ISO 15459-6, c. The employed UDI will be available to all users according to a single set of consistent fair and reasonable terms and conditions. To meet the public health objectives of this guidance and to ensure that medical device user facilities, healthcare providers, regulatory authorities, and others will be able to make efficient and effective use of the UDI System, there could be a need to limit the number of accredited global organizations and available coding systems. 7. The UDI 1. A UDI shall be assigned to the device itself or its package. Higher levels of packaging shall have their own UDI. 2. Shipping containers should be exempted. As an example, UDI is not required on a logistics unit; when a healthcare provider orders multiple medical devices using the UDI or model number of individual devices and the manufacturer places these devices in a container for IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 11 of 19 shipping or to protect the individually packaged devices, the container (logistics unit) is not subject to UDI requirements. 3. The UDI contains two parts: an UDI-DI and an UDI-PI. 4. The UDI-DI (e.g., GS1 GTIN, HIBC-LIC, ISBT-PPIC) should be globally unique at all levels of device packaging. 5. If a lot number, serial number, software version or expiration date appears on the label, they should be part of the UDI-PI. If there also is a manufacturing date on the label, it does NOT need to be included in the UDI-PI. If there is only a manufacturing date on the label, this should be used as the UDI-PI. 6. When a UDI is not assigned to the device at the level of its unit of use, then a UoU UDI-DI should be assigned, to associate the use of a device with a patient. [for example, a UoU UDI- DI would be assigned to an individual electrode when the electrode is distributed in a package of 10 – and lowest level UDI is assigned to that package of 10] 7. Each component, sub-system or accessory that is considered a medical device and is commercially available needs a separate UDI unless the components are part of a convenience, medical procedure, IVD kit or configurable medical device system that is marked with its own UDI. 8. Kits should have their own UDI. 9. The manufacturer assigns the UDI to a device following the relevant coding standard. 10. Any change of one of the following UDID data elements determines the need for a new UDI- DI: a. Brand Name, b. Device version or model, c. Clinical Size (including Volume, Length, Gauge, Diameter), d. Labeled as single use, e. Packaged sterile, f. Need for sterilization before use, g. Quantity of devices provided in a package, h. Critical warnings or contraindications: e.g. containing latex or DEHP. 11. At a minimum, a new UDI-DI is required whenever there is a change that could lead to misidentification of the medical device and/or ambiguity in its traceability. 12. Reprocessors of single use medical devices, remanufacturers, Own Brand/Private Labelers shall create their own, new UDI for the reprocessed, remanufactured, or relabeled medical device which will replace the OEM’s UDI where it exists. 13. Reprocessors of single use medical devices, remanufacturers, Private (Own Brand) Labelers shall retain record of the Original Equipment Manufacturer’s (OEM) UDI. 14. A change of the label to display or modify a UDI-DI should not (in and of itself) require a premarket submission and/or re-registration. Manufacturers may be requested to notify/inform the Regulator. 8. UDI Carrier 1. The UDI Carrier (AIDC and HRI representation of the UDI) shall be on the label or on the device itself and on all higher levels of device packaging. Higher levels do not include shipping containers. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 12 of 19 2. In case of significant space constraints on the UoU package the UDI carrier may be placed on the next higher package level. 3. The UDI Carrier for single use medical devices of risk class A and B packaged and labeled individually does not need to be on its package but rather on higher level of packaging e.g. carton. However when the healthcare provider is not expected to have access (home healthcare settings) to the higher level of device packaging, the UDI should be on its package. 4. Non-prescription medical devices exclusively for retail Point of Sale (POS) do not need to encode Production Identifiers in AIDC on the point of sale package. 5. No particular AIDC methods should be required by a regulatory authority. Globally accepted AIDC methods based on ISO standards that have been adopted by the global organization (e.g., GS1, HIBCC or ICCBBA) shall be used. 6. RFID should comply with open, commercially acceptable, international standards such as ISO 17366:2013 Supply chain application of RFID – Product packaging and be vendor neutral. 7. When AIDC carriers other than the UDI Carrier are part of the product labeling, the UDI Carrier shall be readily identifiable. 8. If linear bar codes are used, the UDI-DI and UDI-PI can be concatenated or non-concatenated in two or more bar codes. All parts and elements of the linear bar code shall be distinguishable and identifiable. 9. If there are significant constraints limiting the use of both AIDC and HRI on the label, the AIDC format shall be favored. However, certain environments or use situations, such as home care, may warrant the use of HRI over AIDC. 10. The HRI format shall follow the rules of the UDI code issuing organization. 11. In case of RFID, a linear or 2D bar code shall also be provided on the label. 12. Medical devices that are reusable should have a UDI Carrier on the device itself. The UDI Carrier of reusable medical devices that require reprocessing between patient uses should be permanent and readable after reprocessing cycles for the intended life of the device. Manufacturers may determine that this may not be possible or warranted on some devices due to size, design, materials, processing, or performance issues. 13. The UDI Carrier should be readable during normal use and throughout intended life of the medical device. 14. If the UDI Carrier is readily readable through the medical device’s package, then the UDI Carrier does not also need to be on the package. 15. A single finished medical device made up of multiple parts that have to be assembled may have the UDI Carrier only on one part. 16. The placement of the UDI Carrier should be done in a way that AIDC method can be accessed during normal operation or storage. 17. The bar code carrier(s) that includes UDI data identifiers “DI” and “PI” may also include essential data for the medical device to operate. The UDI issuing agencies identify these data elements by application identifiers or flag characters. The regulator shall not limit the use of the UDI carrier to only “DI” and/or “PI” data but allow for other relevant data. Example: GS1 General Specification allows for Application Identifier (91) through (99) for company use. This data could be used by the manufacturer as an activation key for a device or IVD analyzer. A GS1 bar code could carry (01) GTIN (17) expiration date (10) LOT (91) internal IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 13 of 19 device activation key. Standard scanners set in the GS1 mode will parse the 4 data elements. (01) is the static DI, (17) and (10) are dynamic PI data. They could be uploaded into hospital inventory systems. (91) would be ignored by the MMIS system but if the product is then placed into use, this AI data could activate the medical device . 9. The UDI Database (UDID) 9.1 General principles of the UDID 1. The UDID shall support the use of all the core UDID data elements. 2. No product commercial confidential information shall be included in the UDID. 3. The manufacturer is responsible for the initial submission and updates to the identifying information and other medical device data elements in the UDID. 4. Appropriate methods/procedures for validation of the provided data shall be implemented. 5. The manufacturers shall periodically reconfirm all the data relevant to their medical devices, except for discontinued medical devices. 6. The core data elements in the UDID shall be accessible to the public free of charge. 7. The presence of the medical device UDI-DI in the UDID does not mean that the medical device is authorized in all jurisdictions. 8. The database should allow for the linking of all the packaging levels of the medical device. 9. The data for new UDI-DI must be available at the time the medical device is placed on the market. 10. Manufacturers should update the relevant UDID record within 30 days when a change is made to an element that does NOT require a new UDI-DI. 11. The UDID shall use HL7 Structured Product Labeling (SPL) standard for data submission and updates. Additional submission means could also be accommodated. 12. The core elements are the minimum elements needed to identify a medical device through distribution and use. Regional or National UDID may contain additional elements; these additional elements should be kept to a minimum. 13. The design of the UDID should support the official languages required in the jurisdictions where the medical device is put on the market. The use of free-text fields should be minimized to reduce the burden of language translations. 14. Data relating to discontinued medical devices shall be retained in the UDID. 9.2 The core UDID data elements All the core UDID data elements are mandatory, unless marked “optional”. “If applicable” means the information is mandatory to be in the UDID if it is on the label. Data elements and their definitions for the UDID are listed below: IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 14 of 19 1. For every device packaging level – the following shall be provided in a related way (for entire packaging hierarchy):  UDI-DI (UDI type, e.g. GS1 GTIN, HIBC-LIC, ISBT-128 PPIC),  Quantity per package configuration: (e.g., each, 10 each, 5 shelf packs),  Additional device identifier(s) (if applicable) e.g. GS1, HIBC, or ISBT-128; 2. The Unit of Use UDI-DI (see section 7.6) code; 3. Manufacturer’s name (if applicable); 4. Manufacturer’s address (if applicable); 5. Manufacturer's customer service contact information (country/region specific, could be multiple);(If applicable) 6. Authorized Representative's name (regional representatives responsible for the medical device) (country/region specific, could be multiple) (if required by the local/regional regulatory authority) (see GHTF/SG1/N55:2009); 7. Authorized Representative's contact information (country specific, could be multiple); 8. Global Medical Device Nomenclature (GMDN) preferred code/term (valid at the time of the UDI submission); 9. Brand Name (if applicable); 10. SaMD version; 11. Device model or version; (see section 10.6) 12. Reference and/or catalogue number (if applicable); 13. How the device is controlled: serial, lot/batch number, and/or expiration date (or manufacturing date) or software version or software released date or ISBT-128 – check boxes (if applicable); 14. Clinical Size (including Volume, Length, Gauge, Diameter) (if applicable) (e.g. 8F catheter); 15. Additional product Description (optional) – Additional clinically relevant information, e.g. radio-opaque; 16. Storage conditions, as labeled or in the IFU (if applicable) – to include temperature range, needs to be refrigerated, relative humidity range, pressure range, avoid direct sunlight; 17. Handling conditions (if different than storage conditions), on the label or in the IFU (if applicable) – to include temperature range, needs to be refrigerated, relative humidity range, pressure range, avoid direct sunlight; 18. Labeled as single use? (Yes/No); 19. Packaged sterile? (Yes/No); 20. Need for sterilization before use? (Yes/No) – if yes, then the method of sterilization should be indicated; 21. Restricted number of reuses (if applicable); 22. License and/or marketing authorization or registration number (if required by the relevant regulatory authority) 23. URL for additional information, e.g. electronic IFU (optional); 24. Critical warnings or contraindications (as labeled) – if a particular regulation requires that the label of the device contains a critical warning or contraindication associated with the use of the device a. [e.g.: Labeled as containing latex? (Yes/No), b. Labeled as containing DEHP? (Yes/No) c. Labeled as MRI compatible? (Yes/No).] 25. Date of discontinuance (referring to devices no longer placed on the market). IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 15 of 19 10. Rules for specific device types 10.1 Implantable devices4 Implantable devices should follow the rules listed below: 1. All unit packs of implantable devices (lowest level of packaging) need to be identified/AIDC marked with an UDI (UDI-DI + UDI-PI); 2. PI should have the following characteristics: a. serial number for active implantable devices, b. serial number for other implantable devices or lot number according to the manufacturer's quality management system; 3. The UDI of the implantable device must be identifiable prior to implantation. For example: tear-away tag bearing the UDI, peel-off labels bearing the UDI affixed to autoclave box holding the implantable device. 10.2 Reusable devices requiring reprocessing between uses 1. The UDI of these products shall be on the device and be readable after each reprocessing; 2. PI characteristics (e.g. lot or serial number) shall be defined by the manufacturer according to the manufacturer's quality management system; 10.3 Non IVD kits 1. The manufacturer of the Kit is responsible for identifying the Kit with a UDI including both UDI-DI and UDI-PI; a. Orthopedic procedure trays whose contents are configured for a specific order are exempted from this UDI requirement. Example: a hospital orders 30 different orthopedic devices for total joint replacement surgery. The 30 devices are delivered to the hospital in a stainless steel box where the devices can be stored and sterilized by the hospital when needed. After a procedure the hospital may replace used parts and re-sterilize the box with its contents; 2. Medical device contents of Kits should have a UDI Carrier on their packaging or on the device itself. Exemptions: a. Individual single-use disposable medical devices within a Kit, whose uses are generally known to the persons by whom they are intended to be used, and which are not intended for individual use outside the context of the Kit do not require their own UDI Carrier. 4 For the definition refer to GHTF SG1/N77:2012. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 16 of 19 Example: an unpackaged sterile syringe within a sterile Kit cannot be used for another procedure due to the lack of a sterile barrier once removed from the Kit; b. Medical devices that are normally exempted from having a UDI Carrier on the relevant level of packaging do not need to have a UDI Carrier when placed within a Kit. 3. Placement of the UDI Carrier on Kits: a. The Kit UDI Carrier is generally affixed to the outside of the packaging; b. The UDI must be readable or in the case of AIDC scan able, whether placed on the outside of Kit package or inside a transparent package. 10.4 IVD Kits IVD kits should follow the rules listed below: 1. The manufacturer of the IVD Kit is responsible for identifying it with a UDI including both UDI-DI and UDI-PI, 2. Medical device contents of IVD Kits should have a UDI Carrier on their packaging or on the device itself, a. The IVD Kit is a device and all aspects of this guidance that is relevant apply to it. If an IVD Kit does not include any components which on their own are considered medical devices the only UDI is the UDI of the kit itself; b. Reagents used in automated systems bear barcodes necessary for their handling and identification by the automated systems. This does not constitute a UDI; c. Individual single-use medical devices packaged within an IVD Kit, whose uses are generally known to the persons by whom they are intended to be used, and which are not intended for individual use outside the context of the IVD Kit do not require their own UDI Carrier; d. Medical devices that are normally exempted from having a UDI Carrier on the relevant level of packaging do not need to have a UDI Carrier when placed within an IVD Kit. 3. Placement of UDI on IVD Kits: a. The IVD Kit UDI is generally affixed to the outside of the packaging; b. The UDI must be readable or in the case of AIDC scan able, whether placed on the outside of the IVD Kit package or inside a transparent package. 10.5 Configurable medical device systems For configurable medical device systems the rules listed below should be followed: 1. A UDI is allocated to the entire, configurable medical device system and is called the System UDI. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 17 of 19 2. The system UDI-DI is allocated to defined groups of configurations, not per configuration within the group. A group of configurations is defined as the collection of possible configurations for a given product line as described in a regulatory file. 3. A system UDI-PI is allocated to each individual system. A later change of a component, sub- systems or accessory of the system does not change the UDI-PI of the system. 4. The carrier of the System UDI should be put on the assembly that most likely does not get exchanged in its lifetime and should be identified as the System UDI. Each component, sub-system or accessory that is considered a medical device and a distributed or supplied unit needs a separate UDI; 6. A new UDI-DI is required when the activities performed results in modifications to a previously marketed device intended for resale leads to a new medical device. 7. A new UDI-DI is not required when the activities performed do not result in a change/modification in performance, safety and/or intended use, of a previously marketed device intended for resale. The activities shall be performed in accordance with the manufacturer’s instructions. 10.6 Software as a Medical Device (SaMD) 10.6.1 UDI Assignment Criteria The UDI should be assigned at the system level of the Software as a Medical Device (SaMD). The version number of the SaMD is considered the manufacturing control mechanism and should be displayed in the UDI-PI. The following change of a SaMD would require a new UDI-DI:  Major SaMD revisions shall be identified with a new UDI-DI; Major SaMD revisions are meant as complex or significant changes affecting 1) the original performance and effectiveness, 2) the safety or the intended use of the SaMD, These changes may include new or modified algorithms, database structures, operating platform, architecture or new user interfaces or new channels for interoperability. The following change of a SaMD would require a new UDI-PI (not a new UDI-DI),  Minor SaMD revisions shall be identified with a new UDI-PI; Minor SaMD revisions are generally associated with bug fixes, usability enhancements (not for safety purpose), security patches or operating efficiency. Minor revisions shall be identified by manufacturer-specific identification methods (e.g. version, revision number, serial number, etc…) 10.6.2 UDI Placement Criteria a. When the SaMD is delivered on a physical medium, e.g. CD or DVD, each package level shall bear the human readable and AIDC representation of the complete UDI. The UDI that is applied to the physical medium containing the SaMD and its packaging must be identical to the UDI assigned to the system level SaMD. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 18 of 19 b. UDI should be provided on a readily accessible screen by the user in an easily-readable plain-text format (e.g. an “about” file or included on the startup screen). c. The SaMD lacking a user interface (e.g. middleware for image conversion) must be capable of transmitting the UDI through an Application Programming Interface (API). d. Only the human readable portion of the UDI is required in electronic displays of the SaMD. The UDI AIDC marking needs not be used in the electronic displays, e.g. about menu, splash screen, etc…; i.e. SaMD not being distributed by the use of physical data carriers (CDs, DVDs or similar) will not carry an AIDC. e. The human readable format of the UDI for the SaMD should include the Application Identifiers (AI) for GS1, and Flag Characters for HIBC, to assist the end user in identifying the UDI and determining which standard is being used to create the UDI. IMDRF/WG/N7FINAL:2013 ____________________________________________________________________________________________ 9 December 2013 Page 19 of 19 11. Annex Category Unpacked UoU  Direct Part Marking (DPM) Base Package Bulk Package Higher package configuration Remarks Single-use MD • IMDRF class A (low-risk) - - DI + PI • Flexibility on possible exemption for PI • IMDRF class B (medium-r.) - - DI + PI • IMDRF classes C+D (high-r.) - DI + PI DI + PI Reusable MD • Require reprocessing between uses • All risk-classes DI + PI DI + PI DI + PI • Not all package levels necessarily exist, e.g.: surgical instruments, intravenous (IV) infusion pumps. Implantable MD • PI = Serial number for active implants • Sterile - DI + PI DI + PI • Usually single packed (1 piece) • Non-sterile Must be identifiable DI + PI DI + PI • Often multiple packed ("n" pieces) • Not necessarily DPM, other technological options allowed to identify the unpacked MD Others • Kits (IVD / non-IVD) - DI + PI DI + PI • Concerns the kit package itself • SaMD DI + PI DI + PI - • Must not necessarily be packed • Configurable MD Systems DI + PI - • AIDC carrier to be placed on a ‚main part‘ (primary mode of action) • OTC exclusively - - DI (linear bar code) • Point-of-Sale scanners can‘t work with PI • OTC + other channels - - DI + PI (non- concatenated) • PI should be presented in a separate AIDC carrier due to Point- of-Sale scanners

Contains Nonbinding Recommendations 1 Global Unique Device Identification Database (GUDID) Guidance for Industry and Food and Drug Administration Staff Document issued on June 27, 2014. The draft of this document was issued on September 24, 2013. This document supersedes Global Unique Device Identification Database (GUDID), June 11, 2014. For questions for the Center for Devices and Radiological Health regarding this document contact UDI Regulatory Policy Support, 301-796-5995, email: udi@fda.hhs.gov. For questions for the Center for Biologics Evaluation and Research regarding this document, contact the Office of Communication, Outreach and Development at 1-800-335-4709 or 240-402-7800. U.S. Department of Health and Human Services Food and Drug Administration Center for Devices and Radiological Health Center for Biologics Evaluation and Research Contains Nonbinding Recommendations 2 Preface Public Comment You may submit electronic comments and suggestions at any time for Agency consideration to http://www.regulations.gov. Submit written comments to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 20852. Identify all comments with the docket number FDA-2013-D-0117. Comments may not be acted upon by the Agency until the document is next revised or updated. Additional Copies CDRH Additional copies are available from the Internet. You may also send an e-mail request to CDRH- Guidance@fda.hhs.gov to receive a copy of the guidance. Please use the document number 1831 to identify the guidance you are requesting. CBER Additional copies of this guidance document are also available from the Center for Biologics Evaluation and Research (CBER), Office of Communication, Outreach and Development, 10903 New Hampshire Ave, Bldg. 71, Room 3128, Silver Spring, MD 20993, or by calling 1-800- 835-4709 or 240-402-7800, by email ocod@fda.hhs.gov, or from the Internet at http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/default.h tm. http://www.regulations.gov/ mailto:CDRH-Guidance@fda.hhs.gov mailto:CDRH-Guidance@fda.hhs.gov Contains Nonbinding Recommendations 3 Table of Contents 1 INTRODUCTION .............................................................................................................................................. 4 2 UNIQUE DEVICE IDENTIFIER (UDI) ............................................................................................................ 5 3.1 GUDID KEY CONCEPTS ............................................................................................................................................ 7 3.1.1 GUDID Account ........................................................................................................................................... 7 3.1.2 Device Identifier (DI) Record ..................................................................................................................... 13 3.1.3 DI Record Life-Cycle .................................................................................................................................. 18 3.2 GUDID MODULES ................................................................................................................................................. 21 3.2.1 GUDID Web Interface ............................................................................................................................... 22 3.2.2 HL7 SPL Submission ................................................................................................................................... 29 3.2.3 Search/Retrieval of Device Information.................................................................................................... 30 4 GUDID SUBMISSIONS AND 21 CFR 11 REQUIREMENTS ...................................................................................... 31 5 CONCLUSION ...................................................................................................................................................... 31 APPENDIX A – GUDID PACKAGE INFORMATION EXAMPLES ....................................................................................... 32 EXAMPLE 1: UNIT OF USE DI + ONE PACKAGE LEVEL ............................................................................................................ 32 EXAMPLE 2: DI ON INDIVIDUAL DEVICE + MULTIPLE PACKAGE LEVELS .................................................................................... 34 APPENDIX B – GUDID DATA ELEMENTS REFERENCE TABLE ................................................................... 36 APPENDIX C – UDI FORMATS BY FDA ACCREDITED ISSUING AGENCY .................................................. 37 APPENDIX D – GUDID ATTRIBUTES MAPPED TO A FICTITIOUS MEDICAL DEVICE LABEL ............... 38 ABBREVIATIONS & ACRONYMS ....................................................................................................................... 39 Contains Nonbinding Recommendations 4 Global Unique Device Identification Database (GUDID) Guidance for Industry and Food and Drug Administration Staff This guidance represents the Food and Drug Administration's (FDA's) current thinking on this topic. It does not create or confer any rights for or on any person and does not operate to bind FDA or the public. You can use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations. If you want to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance. If you cannot identify the appropriate FDA staff, call the appropriate number listed on the title page of this guidance. 1 Introduction The Food and Drug Administration (FDA) is responsible for protecting the public health by assuring the safety, effectiveness, and security of human and veterinary drugs, vaccines and other biological products, medical devices, the nation’s food supply, cosmetics, dietary supplements, and products that give off radiation; and for regulating tobacco products. Section 226 of the FDA Amendments Act (FDAAA) of 2007 and Section 614 of the FDA Safety and Innovation Act (FDASIA) of 2012 amended the Federal Food, Drug, and Cosmetic Act to add section 519(f), which directs the FDA to promulgate regulations establishing a unique device identification system for medical devices along with implementation timeframes for certain medical devices. The Unique Device Identifier (UDI) Proposed Rule was published on July 10, 2012, followed by an amendment, published on November 19, 2012, modifying the implementation time frame for certain devices. In developing the proposed rule, we solicited input from a variety of stakeholders (e.g., manufacturers, global regulatory bodies, the clinical community, patient advocates) to ensure that as many perspectives were incorporated as possible. The UDI Final Rule was published on September 24, 2013. UDI initiatives are also underway globally -- the European Commission released a framework for a UDI System in April 2013; the International Medical Device Regulators Forum (IMDRF) UDI Work Group issued a guidance document on UDI in December 2013. This document is primarily intended for device Labelers1, and provides information necessary for submitting data to the Global Unique Device Identification Database (GUDID). A draft version of this document was 1 The UDI Final Rule (http://www.fda.gov/udi ) defines labeler as “any person who causes a label to be applied to a device with the intent that the device will be commercially distributed without any intended subsequent replacement or modification of the label; and, any person who causes the label of a device to be replaced or modified with the intent that the device will be commercially distributed without any subsequent replacement or modification of the label, except that the addition of the name of, and contact http://www.fda.gov/udi Contains Nonbinding Recommendations 5 released on September 24, 2013 with a 60 day comment period, which ended on November 25, 2013. More than 300 comments were received from 21 entities. In order to provide labelers access to the latest information as soon as it is available, and address sections that received the most comments and questions, sections of this document were previously finalized and released on June 11, 2014. This current iteration of the document finalizes the remaining sections and incorporates sections finalized earlier, in order to provide one complete and final document. Please note that database enhancements may continue to improve user experience, build in better validation rules, and make other necessary changes as we “learn” from the initial roll-out and implementation. We intend to periodically update this document to reflect system changes and enhancements. FDA's guidance documents, including this guidance, do not establish legally enforceable responsibilities. Instead, a guidance describes the Agency's current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required. 2 Unique Device Identifier (UDI) The “unique device identifier” (UDI) should be created and maintained by device labelers based on global device identification standards managed by FDA-accredited Issuing Agencies2,3. As of the publication date of this document, we have accredited three issuing agencies – GS1, HIBCC and ICCBBA. The ‘UDI Formats by FDA Accredited Issuing Agency4 document, provides the standard UDI formats for the three issuing agencies. A UDI is required to appear on the label of every medical device, and every device package, unless excepted. This includes combination products that contain a device constituent part; convenience kits; in vitro diagnostic products; human cells, tissues, and cellular and tissue-based products (HCT/Ps) regulated as devices; and stand-alone software5. The UDI is composed of two parts: • Device Identifier (DI) - a mandatory, fixed portion of a UDI that identifies the labeler and the specific version or model of a device; and • Production Identifier(s) (PI) – a conditional, variable portion of a UDI that identifies one or more of the following when included on the label of a device, unless excepted: o the lot or batch number within which a device was manufactured; o the serial number of a specific device; o the expiration date of a specific device; o the date a specific device was manufactured; o and, for an HCT/P regulated as a device, the distinct identification code required by 21 CFR 1271.290(c)6. information for, a person who distributes the device, without making any other changes to the label, is not a modification for the purposes of determining whether a person is a labeler.” 2 Refer to the UDI Final Rule (http://www.fda.gov/udi ) for details on issuing agencies and their role in UDI assignment. 3See 21 CFR 801.57(c ) and visit http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Databases/ucm161456.htm for information regarding continued use of National Health Related Items Code (NHRIC) and National Drug Code (NDC). 4 See “UDI Formats by FDA-Accredited Issuing Agency” document, available on www.fda.gov/udi 5 Stand-alone software version number may be represented as Lot or Batch number production identifier. 6 21 CFR 1271.290(c) requires that the manufacturer of each HCT/P assign and label the HCT/P with a distinct identification code that allows the manufacturer to relate the HCT/P to the donor and to all records pertaining to the HCT/P. The distinct identification code may take the form of a donation identification number, serial number, lot number, or a combination of these production identifiers. In http://www.fda.gov/udi http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/Databases/ucm161456.htm http://www.fda.gov/udi Contains Nonbinding Recommendations 6 Therefore, UDI = DI + PI. The DI will serve as the primary key and can be used to look up information about the device in the GUDID. Any identifiers beyond those specified in this document are outside the scope of the FDA regulated UDI. Note that the UDI of a class I device is not required to include a PI. Further, a class I device that bears a Universal Product Code (UPC) on its label and device packages is deemed to have met the UDI labeling requirements. Finally, Class I devices that FDA has by regulation exempted from the good manufacturing practice requirements (other than recordkeeping requirements) do not need a UDI. See 21 CFR 801.30(a)(2). Labelers are required to enter the DI along with additional device attribute information to the GUDID, as specified in the final rule, unless subject to an exception or alternative. While we expect GUDID DI submissions to occur as soon as practicable, for device versions or models initially entering commercial distribution, the DI records for such devices should be in the published state no later than fifteen calendar days from the initial date that version or model is introduced into commercial distribution. 3 Global Unique Device Identification Database (GUDID) The GUDID serves as the repository of key device identification information. The GUDID contains ONLY the DI, which serves as the primary key to obtain device information in the database. PIs are not submitted to or stored in the GUDID; the GUDID contains only production identifier flags to indicate which PI attribute(s) are on the device label, unless excepted. The GUDID includes all of the data elements required by 21 CFR 830.310. The GUDID also includes certain ancillary administrative data used to develop and maintain the GUDID and to facilitate integration of DI information with internal FDA systems. A complete list of GUDID data elements and descriptions are provided provided in the ‘GUDID Data Element Reference Table7. For those data attributes in the GUDID that appear in medical device labeling, the attribute values submitted to GUDID should be consistent with their representation in the labeling. See example in Appendix D, which maps some GUDID attributes to a fictitious device label. The design principles guiding GUDID development includes the following: • Standards-based submission with two options: o Structured input via the GUDID Web Interface – requires manual data entry and is geared for low volume submitters. o Health Level 7 (HL7)8 Structured Product Labeling (SPL)9 submission via the FDA Electronic Submissions Gateway (ESG)10 – allows for submission via xml files and is geared for high volume submitters. the GUDID, labelers of HCT/Ps regulated as medical devices should select the appropriate type of production identifier that appears the label of the device. 7 See GUDID Data Elements Reference Table, available on www.fda.gov/udi 8 HL7 is a standards development organization, whose mission is to provide messaging standards for interoperability, exchange, management, and integration of data that supports clinical patient care and the management, delivery, and evaluation of healthcare services. Visit http://www.hl7.org for more information. 9 Structured Product Labeling (SPL) is a HL7 standard for the exchange of product information using extensible markup language (XML). http://www.fda.gov/udi http://www.hl7.org/ Contains Nonbinding Recommendations 7 • Standards-based data repository with controlled vocabularies including: o Dun & Bradstreet (D&B) Number (DUNS)11 o Global Medical Device Nomenclature (GMDN)12 o FDA Product Codes • Free and public access to the device information in GUDID via public search; download capability is planned for the future. 3.1 GUDID Key Concepts The next few sections present an overview of GUDID key concepts such as GUDID account and user roles, the device identifier record, and the device identifier record life-cycle. Note that these concepts apply to both GUDID submission options – Web Interface and HL7 SPL xml file submission. 3.1.1 GUDID Account Labelers that are required to submit information to the GUDID should first request a GUDID account. This section presents an overview of the GUDID account, the user roles, preparatory steps to obtain a GUDID account, how to request a GUDID account and how to manage account changes. The structure of the GUDID Account and the different user roles are depicted in Figure 1. 10 FDA ESG enables the secure submission of regulatory information. For more information, please visit: http://www.fda.gov/esg 11 Data Universal Numbering System or D-U-N-S® Number is a unique nine-digit identification number assigned and managed by Dun & Bradstreet to business entities. For more information, visit http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162544.htm 12 Global Medical Device Nomenclature (GMDN) is system of internationally agreed descriptors used to identify medical device products and is managed by the GMDN Agency. Visit: http://www.gmdnagency.com/default.aspx http://www.fda.gov/esg http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162544.htm http://www.gmdnagency.com/default.aspx Contains Nonbinding Recommendations 8 Figure 1: GUDID Account and User Roles Contains Nonbinding Recommendations 9 A Labeler Organization may have one or more GUDID accounts. • GUDID utilizes DUNS numbers to enable identification of labeler organizations using a uniform standard and process. The DUNS number is an important component of the FDA Unique Facility Identifier System, along with a Geocode, which specifies the exact location of the facility (GUDID does not collect Geocodes). • Labelers should manage their company information via the DUNS number and GUDID pulls company name and address from the D&B DUNS database. • Each GUDID account is identified by the Organization DUNS Number. o This DUNS number represents the labeler’s view of the highest corporate level in the labeler organization; it may be the headquarters DUNS number, or the parent DUNS number for the labelers included in the GUDID account. o Please ensure that the name and address in the D&B DUNS database is accurate, as this number is used to identify the labeler organization in GUDID; company name and address are pulled from the DUNS database. o The organization DUNS number serves as the primary key for the GUDID account. Once used, it cannot be reused to create another GUDID account. o The organization DUNS number can be used as a Labeler DUNS number (see below). • Each account should have only one Regulatory Contact. o As noted in 21 CFR 830.320(a), a Regulatory Contact13:  Is the individual who serves as the point of contact to us on matters relating to the identification of medical devices marketed by the labeler; he/she is responsible for ensuring the labeler organization meets GUDID submission requirements.  Is the highest point of contact for the labeler organization, i.e., we may first contact the GUDID Coordinator for issues related to the data submitted to GUDID, and if the issue is not resolved, bring it to the attention of the Regulatory Contact.  Does not have functional user role in GUDID i.e, no user-name or password to access GUDID.  Can also serve as GUDID Coordinator and Labeler Data Entry user, if so desired (see below); both of these user roles would have a separate user name and password to access GUDID. o You may choose to use a third-party to serve as the Regulatory Contact for GUDID as described in 21 CFR 830.320(a); you should inform us of your intent to do so during the GUDID account request process via a letter on your company letterhead, signed by a responsible official from your organization. • Each GUDID account should have one or more labelers, identified by Labeler DUNS numbers. o Device information would be submitted for the Labelers identified in the GUDID account. o Each device record should be associated to a Labeler DUNS number, and is used to pull the labeler company name and address from the D&B DUNS database. o To ensure data consistency the company name associated to the Labeler DUNS number should match the company name that appears on the device label. Ideally the address associated with the DUNS number should also match the address on the device label, but since address is not displayed to the GUDID public user, this is not a requirement; however, labelers are encouraged 13 GUDID Account user contact information provided is for FDA internal use only; not available via GUDID public search and retrieval. Contains Nonbinding Recommendations 10 to work towards this model for new products and when making changes to existing products as appropriate. o Organization DUNS number can be used as Labeler DUNS number. o Labeler DUNS number, once used, cannot be reused in any other GUDID account. • Each GUDID account should have one or more Coordinators13. o Each Coordinator would be assigned one or more Labeler DUNS numbers, in a given GUDID account. o Coordinators manage the GUDID account for their designated Labeler DUNS numbers. Responsibilities should include:  Create Labeler Data Entry (LDE) User account(s) (see below).  Assign Labeler DUNS number(s) to LDE(s).  Create LDE User role for a third-party (see below), if so desired.  Serve as Regulatory Contact, if so desired.  Serve as LDE user, if so desired; separate user name and password is provided for the LDE user role.  Serve as the first point of contact and respond to FDA inquiries related to GUDID data quality, incorrect or inconsistent data, and other submission/data specific questions. o A given Labeler DUNS Number can be assigned to more than one Coordinator (see Figure 1, Labeler DUNS Number 3 is assigned Coordinator 1 and Coordinator 2). The Coordinators would then share responsibility for DI records associated to that Labeler DUNS number. • Each GUDID account should have one or more LDE Users13. o Each LDE user is assigned one or more labelers, identified by Labeler DUNS numbers, in a given GUDID account. o An LDE user:  Is responsible for data entry, submission, and management of device identification information for their designated Labeler DUNS into the GUDID.  Can serve as Regulatory Contact, if so desired.  Can serve as Coordinator user, if so desired; separate user name and password is provided for the Coordinator user role. o A given Labeler DUNS Number can be assigned to more than one LDE user. The LDE users would then share responsibility for DI records associated to that Labeler DUNS number. The labeler has the option to designate third-party submitters for GUDID submissions. A third-party submitter is a company/individual (contractor, vendor) authorized to submit GUDID information on behalf of the labeler. The third-party may submit data on behalf of the labeler, but the labeler is ultimately held responsible for the information submitted to GUDID. • Each GUDID account may have zero or more third-party submitters. • Web Interface submission option – a third-party may use the GUDID Web Interface to enter data for the labeler. You, the labeler, may choose to request the Coordinator user role for the third-party (request sent to FDA, see section 3.1.1.2); you may provide the third-party with LDE user access. • HL7 SPL submission option – the third-party may: o Provide software solution/tool to generate the HL7 SPL xml file; you, the labeler, would then submit the file via the FDA ESG. or, o Provide end-to-end solution to the labeler, i.e., generate the HL7 SPL xml file, and submit it via the FDA ESG for the labeler. In order to enable a third party to submit to GUDID via the ESG, the following should be noted: Contains Nonbinding Recommendations 11  You, the labeler, should identify the third-party by providing the third-party DUNS number during your GUDID account request. The third party is associated to your labeler account. By identifying the third-party, you are authorizing the third-party to submit GUDID information on your behalf.  GUDID HL7 SPL submissions sent via the ESG by a third party not associated to a GUDID account are rejected. Note that GUDID Regulatory Contact, Coordinator and LDE user contact information provided by labeler organizations is used for internal FDA purposes only; not available via GUDID public search and retrieval. Submission of device information to GUDID requires establishment of a GUDID account, regardless of the submission option chosen –via Web Interface or via FDA ESG as HL7 SPL xml files. Please note that the GUDID account is not by submission type, i.e., a separate GUDID account is not needed for each submission option. The account identifies the labeler in GUDID and enables submission of device information via both options. See section 3.1.1.2 for detailed description of the account establishment process. Search and retrieval of GUDID information does not require a GUDID account. 3.1.1.1 Preparatory Steps Prior to Requesting a GUDID Account Prior to requesting a GUDID account, labeler organizations are encouraged to ensure the following: • Familiarize yourself with the two submission options available – GUDID Web Interface and HL7 SPL xml file submission. • Identify the DUNS Numbers to be used for your GUDID account. o If your company does not have a DUNS number, you can obtain one free of charge from D&B. Please note that this may take up to 30 business days; please plan accordingly. o Expedited options to obtain a DUNS number are available for a nominal fee. o Please visit http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162544.htm for more information. • Ensure the company name and address associated to the DUNS number is correct; if any changes are necessary, please update your information in the D&B DUNS database before requesting a GUDID account. • Identify individuals for the various user roles in GUDID -- Regulatory Contact, Coordinator(s) and LDE user(s). o Note that the one individual can take on multiple GUDID user roles. o If you plan to use a third-party to serve as the Regulatory Contact for GUDID as described in 21 CFR 830.320(a), please inform us of your intent to do so during the GUDID account request process via a letter on your company letterhead, signed by a responsible official from your organization. • Identify an individual to request the GUDID account; and, once the account is established, to manage all account changes. • Identify third-party submitters, if applicable. o Obtain third-party DUNS number after ensuring that they have verified their information in the DUNS database as accurate. http://www.fda.gov/ForIndustry/DataStandards/StructuredProductLabeling/ucm162544.htm Contains Nonbinding Recommendations 12 3.1.1.2 GUDID Account Request Process Once the necessary information is gathered, a GUDID account request may be submitted to us. Visit http://www.fda.gov/udi for information on how to submit the request. The following information should be provided when requesting a GUDID Account: • Labeler Organization DUNS Number – this DUNS number represents the labeler’s view of the highest corporate level in the labeler organization; it may be the headquarters DUNS number, or the parent DUNS number for the Labelers included in the GUDID account. • Labeler Organization Name – this is used for verification purposes only; GUDID obtains company name and address from the D&B DUNS database. • Regulatory Contact information – name, email, phone, physical address. • Labeler DUNS for the GUDID Account – as indicated earlier in Section 3.1.1, the company name associated to the Labeler DUNS number should match the labeler name as it appears on the device label; ideally, the company address associated to the DUNS number should also match the address on the label, but since address is not displayed to the GUDID public user, this is not a requirement for data consistency. • Coordinator Information: o Contact information – name, email, phone o List of Labeler DUNS that is the responsibility of the Coordinator; if there are multiple Coordinators, please specify the DUNS that each Coordinator is responsible for in GUDID. • Third-party DUNS numbers, if applicable • Indicate the preferred submission option – Web Interface or HL7 SPL or both o HL7 SPL submitters should first complete testing as specified in the HL7 SPL Implementation specification, prior to submitting to production GUDID. Therefore, HL7 SPL submitters are first provided with a test GUDID account. Note that GUDID Regulatory Contact, Coordinator and LDE user contact information that you provide is used for internal FDA purposes only; not available via GUDID public search and retrieval. Once we receive the GUDID account request, the information is reviewed. We may contact the individual requesting the account with any questions such as discrepancies with labeler company name and address associated to DUNS numbers, third party information etc.. Once all issues are resolved, we create the GUDID account using the GUDID Web Interface; the Coordinator receives login information and a temporary password via a system generated email. Each GUDID account will have, at a minimum: • one Regulatory Contact • one Labeler DUNS number • one Coordinator – for submitters who are using the HL7 SPL submission option, the Coordinator user is optional. Once a GUDID account is created: • The Web Interface submitter may login and begin using GUDID14. 14 For detailed information on logging in and using GUDID for each user role, please refer to the Global Unique Device Identification Database (GUDID) User Manual, available at -- http://www.fda.gov/udi Contains Nonbinding Recommendations 13 o Coordinator may access the system via their temporary login and password to create LDE Users o Coordinator should have the following information to create an LDE user account:  LDE user information: name, email, phone  List of labeler DUNS to be assigned to the LDE user o Once accounts are created, the LDE user receives temporary login and password via system generated email. • HL7 SPL ONLY submitters, please refer to section 3.2.2 for additional details. 3.1.1.3 GUDID Account Changes To make changes to an existing GUDID account, please contact the FDA UDI Help Desk by visiting www.fda.gov/udi . We recommend that you identify an individual in your organization to manage GUDID account changes. Account changes may include: • Update Regulatory Contact information • Add/update Coordinator information • Change assignment of Labeler DUNS to Coordinators • Add Labeler DUNS • Add/update third-party submitter information • Account changes related to mergers/acquisitions that may impact DI records – current version of GUDID has not implemented capability to handle all use-cases surrounding mergers/acquisitions. We are actively working to identify requirements for future system implementation. We request that you please contact us if you anticipate a merger/acquisition that may impact your DI records, so we can work proactively to address your situation. 3.1.2 Device Identifier (DI) Record Recall from Section 2, that a UDI = Device Identifier (DI) + Production Identifier (PI). The DI, together with associated data attributes15, constitutes a DI Record in the GUDID, and contains identifying information for a particular device version or model. Please note that information presented in this section applies to both GUDID submission options – Web Interface and HL7 SPL xml file submission. The following are key characteristics of a DI Record in GUDID: • GUDID will only contain the DI; the PI is never part of the GUDID. However, the GUDID will contain production identifier flags, to indicate which PI attribute(s) (lot or batch number, serial number, expiration date, manufacturing date and donation identification number) appear on the label of the device, unless excepted. • Primary DI: Each DI record will have a Primary DI, which is the primary key for the record. This is the DI of the lowest level of a medical device package containing a full UDI. The lowest packaging level is also the base package. http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/GlobalUDIDatabaseGUD D/UCM396841.pdf 15 See GUDID Data Elements Reference Table, available on www.fda.gov/udi for a list of data attributes http://www.fda.gov/udi http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/GlobalUDIDatabaseGUDID/UCM396841.pdf http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/GlobalUDIDatabaseGUDID/UCM396841.pdf http://www.fda.gov/udi Contains Nonbinding Recommendations 14 o Under 21 CFR 830.40(a), a version or model of a device may be identified using only one DI from a given FDA accredited issuing agency. The same version or model may be identified by UDIs from other FDA accredited issuing agencies; labelers must identify the DI from one issuing agency as the Primary DI in GUDID and the DIs from other issuing agencies may be listed as Secondary DIs (see below). • The DI record may also contain additional device identifiers: o Secondary DI: An identifier that is an alternate (secondary) lookup for a medical device that is issued from a different FDA accredited issuing agency than the primary DI. o Unit of Use DI: A virtual identifier assigned to an individual medical device when a UDI is not labeled on the individual device at the level of its unit of use. Its purpose is to associate the use of a device to/on a patient when a base package contains more than one device. The package configuration example in Appendix A, Figure 1, includes a Unit of Use DI. o Direct Marking DI: An identifier that is permanently marked directly on the medical device; can be the same as or different from the Primary DI; only applicable to devices subject to Direct Marking requirements under 21 CFR 801.45. o Package DI: A device identifier for the package configuration that contains multiple units of the base package (does not include shipping containers16).  Package information for a particular version or model of a device is part of the DI record. See section 3.1.2.1 below for more information. Note that the current implementation of GUDID does not include the ability to capture the previous DI as required under 21 CFR 830.310(b)(2). This may be included in a future implementation of GUDID. Labelers will be provided sufficient notice and time to incorporate changes into their source systems. • All DIs will be checked for uniqueness in the GUDID. Once used, a DI can never be reassigned to another device, even if the original device is no longer in commercial distribution. o When Commercial Distribution End Date <= today (i.e. today or a date in the past), the device will be considered no longer held or offered for sale by the labeler. The device may or may not still be available for purchase in the marketplace. o The device will still be in the database and available via public search, but will be noted as “Not in Commercial Distribution”. Each DI record will be subject to GUDID business rules to ensure data quality. GUDID business rules for each data attribute are provided in the GUDID Data Elements Reference Table, available on www.fda.gov/udi. Business rules include the following: • Required data attributes must be provided – see GUDID Data Elements Reference Table, available on www.fda.gov/udi for a list of required attributes. While some fields in GUDID are not required, we recommend that labelers populate all fields applicable to the device, when the information is available in device labeling. For example, while Device Description is not required in GUDID, if you populate this attribute, users will benefit from the information. • Validation of specified attributes. For example, the FDA Listing Number provided must be valid. • Data constraints on specified attributes. For example, Publish Date must always be >= today (i.e., today or a date in the future). 16 The UDI Final Rule defines a Shipping Container as a container used during the shipment or transportation of devices, and whose contents may vary from one shipment to another. http://www.fda.gov/udi http://www.fda.gov/udi Contains Nonbinding Recommendations 15 • System rules that determine available user actions based on the status of the DI record. For example, only Unpublished and Published DI records can be copied. Sections 3.1.3.1 and 3.2.1.1 provide system rules for each DI record state. 3.1.2.1 Package Information in GUDID According to 21 CFR 801.3, a device package is a fixed quantity of a particular version or model of a device. In order to adequately identify a device throughout distribution and use, the various package configurations, i.e. each different type of package, must have a unique identifier, 21 CFR 801.20(a)(2). Thus, if a device is sold in individual device packages, that are sold in boxes of thirty (30) device packages, that are sold in cartons that contain twelve (12) boxes of thirty (30) device packages, a different DI would be required to appear on the individual device package, on the box of thirty packages, and on the carton of twelve boxes of thirty device packages. Following are key points to note regarding package information in GUDID: • The Primary DI number for a DI record identifies the lowest level of medical device package containing a full UDI; also known as the base package. The Primary DI, therefore, is also the base package DI. • The Device Count attribute provides the number of medical devices in the base package. • Package configurations of the base package are part of the base package DI record. • Package configurations inherit base package attribute values. Therefore, Package DIs do not need their own DI record; instead package information may be entered in the Package DI section of the Primary DI record for that device. Attributes specific to each package may be entered and include: o Package Device Identifier – DI for the particular package configuration (does not include shipping containers). o Contains DI Package –DI for the lower level package configuration contained within that particular package configuration (what is the DI for the package inside this package?). o Quantity per Package – number of packages contained within the particular package configuration with a unique DI (how many packages are inside this package?). o Package Type – optional text to describe the outer packaging of the product (box, carton, etc.) and enables users to understand higher-level packaging configurations. o Package Discontinue Date – indicates the date a particular package configuration is discontinued by the labeler. o Package Status –indicates whether the package configuration is in commercial distribution as defined under 21 CFR 807.3(b); auto-populated by the system based on Package Discontinue Date:  If Package Discontinue Date > today (i.e., a date in the future) or null, then Package Status = “In Commercial Distribution”  If Package Discontinue Date =< today (i.e., today or a date in the past), then Package Status = “Not In Commercial Distribution” Figure 2 provides a package configuration example for GUDID where the DI is on the individual device with one package level. • Oral/enteral syringe, each with Primary DI 00884838035683 and Device Count = 1. • Box of 100 syringes, with Package DI 30884838035684 (contains 100 units of Primary DI 00884838035683). Contains Nonbinding Recommendations 16 • Package Discontinue Date is blank (null); therefore Package Status is set to “In Commercial Distribution.” Package 30884838035684 inherits all attribute values of base package 00884838035683, except for the attributes specific to 30884838035684, as shown in the table below. Base Package Primary Device Identifier Device Count 00884838035683 1 Package Information Package DI Quantity per Package Contains DI Package Package Type Package Discontinue Date Package Status 30884838035684 100 00884838035683 Box In Commercial Distribution Figure 2: Package Configuration Example17 Additional examples of package configurations, along with attribute values pertinent to packages, are provided in Appendix A. 3.1.2.2 Global Medical Device Nomenclature (GMDN) Each DI record in GUDID requires entry of at least one GMDN Preferred Term (PT) codes. The GUDID business rules allow more than one GMDN term to be assigned per DI record, but this allowance was developed for the rare occurrence where more than one term is needed to accurately describe the device. It is expected that most records would assign one, and only one, GMDN term. 17 Device Identifiers used in the example are fictitious. Please refer to “UDI Formats by FDA Accredited Issuing Agency” in Appendix C for correct format of the DI numbers by FDA Accredited Issuing Agencies MZW Typewritten Text MZW Typewritten Text MZW Typewritten Text MZW Typewritten Text MZW Typewritten Text MZW Typewritten Text Package Configurations of the Base Package MZW Typewritten Text MZW Typewritten Text MZW Typewritten Text Contains Nonbinding Recommendations 17 GMDN is a system of internationally agreed upon descriptors used to represent common device types for the purposes of grouping or categorization. GMDN terms, managed by the GMDN Agency, have been developed over the past 20 years as a vocabulary that represents the whole medical device arena, including such specialties as dental products, laboratory equipment, in vitro diagnostics, and biologic devices with cellular or tissue origins. Each GMDN Preferred Term (PT) has 3 components: Preferred Term Code (5-digit number), Preferred Term Name, and Preferred Term Definition. GMDN is maintained and updated to represent the evolving medical device field; meaning PT names and Definitions may be edited, new terms may be developed and out-dated terms may be made obsolete. The GUDID represents the first implementation of the Global Medical Device Nomenclature (GMDN) within FDA. To obtain access to the GMDN vocabulary and to select GMDN terms for submission to the GUDID, companies should first become a member of the GMDN Agency. Visit http://www.gmdnagency.com for details. While GMDN Membership is not required (see ‘GUDID Search Module’ below), the GMDN Agency offers benefits and services with its Codes that aren’t available through the free-access GUDID search module. Prior to submission of DI records to the GUDID, ensure the following: • Identify and obtain appropriate GMDN terms for devices requiring GUDID submission. • NOTE: if a device requires the development of a new device category, or a new Preferred Term, this requires time, so please plan accordingly. o When selecting a GMDN term, be advised that GMDN Definitions may contain language with a specific regulatory definition or implication to FDA. Assignment of a GMDN term with such language in the name or definition to your DI record does not imply agreement by FDA to a particular regulatory interpretation for your device. • If your company has GMDN terms that are currently in use, use the GMDN Agency as a resource to evaluate the following: o Term fitness – determine if this GMDN term or device category best represents the device o Term Status -- determine if terms are “active” or have been made “obsolete” o If your company’s Codes have been designated as “obsolete,” identify replacement terms by searching the GMDN vocabulary or contacting the GMDN Agency for assistance. o NOTE: GMDN terms accepted by other regulatory authorities may not be acceptable terms for GUDID DI record submission. The GUDID implementation of GMDN recognizes only ‘active’ GMDN terms. • Submit only active GMDN terms to the GUDID. During submission of DI records: • For DI record entry via the web user interface, the GMDN PT Code should be used to assign the GMDN term to the record; the Name and Definitions fields would be auto-populated. (For submission of GMDN terms in HL7 SPL xml files, see GUDID HL7 SPL Implementation Specification files, available at www.fda.gov/udi ) Maintaining GMDN Codes in DI Records: • It is the responsibility of labelers to make sure their DI record information is accurate and up-to-date. If you maintain a membership with GMDN, the Agency notifies you when your terms have been modified or made obsolete. If not, it would be your responsibility to update your GMDN terms periodically or when required to by validation rules (see next bullet). • If a GMDN term becomes obsolete, the labeler/LDE should update the GMDN term in order to pass validation when updating any other DI record attribute. An obsolete GMDN term doesn’t require an http://www.gmdnagency.com/ http://www.fda.gov/udi Contains Nonbinding Recommendations 18 update, in and of itself, but when editing other attributes the DI record would not pass validation/review without an active GMDN term. • Once a DI record has been published in the GUDID with an active GMDN term, that assignment remains until deliberately changed by the labeler/LDE. There is no automatic update of GMDN terms within the GUDID. • If GMDN information changes, the updated information must be submitted within 10 business days of the change per 21 CFR 830.330(b). GUDID GMDN Search Module As stipulated in the Final UDI Rule [78 FR 58786], FDA has developed a GUDID search module, “Find FDA PT Codes” that enables users to select a GMDN term to be used in their GUDID submission until a GMDN Code can be obtained from the GMDN Agency. The FDA Preferred Term (PT) Codes are a 4-letter code assigned to each GMDN term, in place of the GMDN Code. The FDA PT Code is accepted into the GMDN Code attribute field in the DI Record and the GMDN Name and Definitions are auto-populated, as from GMDN Codes. The data entry requirement is met by entering a GMDN Code (5-digit) or FDA PT Code (4- letter); there is no need to enter both. Please do not attempt to enter a GMDN Code and an FDA PT Code for the same GMDN term. Since the FDA PT Codes only apply to GUDID DI Record entry and cannot be used in place of GMDN Codes for any other system, we encourage GUDID submitters to obtain the GMDN code and replace the FDA PT code as soon as possible. FDA PT Codes are also accepted in HL7 SPL xml document submission, but the same limitations apply. (For more details on GMDN entry in HL7 SPL xml files, see GUDID Draft HL7 SPL Implementation Specification, v1.1 at www.fda.gov/udi ) The Find FDA PT Code module can be found on the GUDID homepage after logging-in with a username and password. The Find module is separate from the DI record data entry module. There is no access to the ‘Find FDA PT Codes’ module from within a DI record. An LDE User should first search and select a GMDN PT Name (and associated FDA PT Code) for a specific device; then enter a DI record and use the FDA PT Code to assign the GMDN Name and Definitions to the DI record. Labelers in need of assistance with term selection or new term development are encouraged to contact the GMDN Agency, www.gmdnagency.com. NOTE: Representation of GMDN in Appendix D, Figure D1, a Fictitious Medical Device Label is for illustration purposes ONLY. GMDN PT Name and Definition are NOT expected to appear on the label of a device. 3.1.3 DI Record Life-Cycle The GUDID DI Record Life-Cycle comprises the various states of a DI record and the associated business rules and functionality available to a user. Please note that the DI record life-cycle applies to both GUDID submission options – Web Interface and HL7 SPL xml file submission; where there are differences due to the type of submission, they have been noted. 3.1.3.1 DI Record States A DI record is in one of three DI record states at any given time. The DI record state determines the applicable business rules and the GUDID functionality available to users. http://www.fda.gov/udi http://www.gmdnagency.com/ Contains Nonbinding Recommendations 19 A new DI record may be saved in one of the following three DI record states: Draft DI record, Unpublished DI record, or Published DI record. Only DI records in a published state will be considered to have met the GUDID submission requirements under 21 CFR 830 Subpart E. Draft DI Record: enables you to prepopulate and save a DI record with the available information via the GUDID Web Interface. Additionally, users may also create Draft DI records to get familiar with creating and saving DI records in GUDID; however, please do not Submit records for publishing when created solely for the purpose of familiarizing yourself with the system. Merely creating and saving Draft DI records does not fulfill your GUDID submission requirements under 21 CFR 830, subpart E. Please note that the Draft DI record state is only applicable to the GUDID Web Interface option. HL7 SPL submissions cannot be submitted as Draft DI records. A Draft DI record: • does not have to pass any business rules prior to being saved as a Draft DI record. • can be edited an unlimited number of times via the GUDID Web Interface. • can be saved in the Draft DI record state for 180 calendar days; the record will be “purged”, i.e., permanently removed from the GUDID, after 180 calendar days of inactivity. o Please note that the 180-day cycle resets and starts over each time the Draft DI record is edited and re-saved as a draft. • can only be viewed/edited by the LDE user who created the record. • is not available for public search and retrieval. A Draft DI record must pass Review, i.e., pass business rules before it can be Submitted to GUDID. Upon submission, the record then can be in Unpublished or Published state based on the Publish Date: • Unpublished state means Publish Date > today (i.e., a date in the future). • Published state means Publish Date =< today (i.e., today or a date in the past). Unpublished DI Record: enables users to complete a DI record and Submit it to GUDID prior to the required date. Saving unpublished DI records alone does not fulfill your GUDID submission requirements under 21 CFR 830, subpart E. An Unpublished DI record: • has passed all business rules, i.e., has passed Review. • has not reached the Publish Date (Publish Date > today (i.e., a date in the future)). • can be edited unlimited number of times; however, each time the record is edited, the record must pass business rules, i.e., Review again. • can be copied to create new DI records, enabling reduction of data entry time; all attributes except for the Primary DI number and package information are copied. • can be viewed by the FDA and LDE users assigned to the Labeler DUNS associated to the given DI record. FDA may review your Unpublished DI records for data quality assessment and contact you with questions. • is not available for public search and retrieval. • will be checked by an automated GUDID nightly process, and when Publish Date = today, the record will move to the Published DI record state. Contains Nonbinding Recommendations 20 Published DI Record: a DI record that is available for search and retrieval by the public. We will consider you to have complied with the requirements of 21 CFR 830.330 on the date that the DI record is saved in GUDID in the published state. A Published DI record: • has passed all business rules, i.e., has passed Review. • has Publish Date =<today (i.e., today or a date in the past). Please note that a DI record entered with Publish Date = today, will be available for public search immediately. • can be copied to create new DI records, enabling reduction of data entry time; all attributes except for the Primary DI number and package information are copied. • is available for public search and retrieval. • is subject to editing limitations as determined by the Grace Period. The Grace Period is 7 calendar days and starts the day after the DI record is published. Publish Date Grace Period Start Date Grace Period End Date Monday, July 15, 2013 Tuesday, July 16, 2013 Monday, July 22, 2013, 11:59 PM o Editing within-the-Grace-Period  all attributes, except Publish Date can be edited. o Editing after-the-Grace-Period will be limited  New DI trigger attributes cannot be edited; these are core attributes which, when changed, no longer represent the same device and require a new DI.  certain attributes would have limited editing capability; a complete list of edit rules are available in the Data Elements Reference Table, available on www.fda.gov/udi . For example:  FDA Premarket Submission Number: - can ‘Add’ Premarket Submission Numbers after the grace period - cannot ‘Edit’ or ‘Delete’ existing values after the grace period  in the rare situation where New DI trigger attributes or attributes with limited editing need to be edited after-the-grace-period18, you may contact the FDA UDI Help Desk and request assistance.  FDA Staff will review your request and move your record to the Unpublished DI record state  You may make the necessary edits and submit the DI record again to be published. Please note that Published DI records for devices removed from commercial distribution will remain in the published state and will be available for public search and retrieval. It is the responsibility of the labeler to update the DI records for discontinued devices. The Commercial Distribution Status will be auto-populated by the system based on Commercial Distribution End Date as shown below. • When Commercial Distribution End Date> today (i.e., a date in the future) or null, Commercial Distribution Status = “In Commercial Distribution” • When Commercial Distribution End Date =<today (i.e., today or a date in the past) , Commercial Distribution Status = “Not In Commercial Distribution” 18 Edits to New DI trigger attributes and attributes with limited editing after-the-grace-period is expected to be an extremely rare occurrence. Labelers should ensure their DI record data is accurate before the record moves to the published state. http://www.fda.gov/udi http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/ucm368904.htm Contains Nonbinding Recommendations 21 The table below provides a summary of the three DI record states: DI Record State Description System Save duration Possible Actions on the DI Record Available via Public Search? Draft DI record Saved DI record that has not passed business rules Please note that HL SPL Submissions cannot be submitted as Draft DI records. This state is only applicable to the GUDID Web Interface option. Purged after 180 calendar days of inactivity; if edited and resaved as draft, the 180-calendar day cycle resets and starts over --Unlimited editing --Resave as Draft --Delete Draft --Must pass business rules and be Submitted to move to other DI record states --No --only available to the LDE user who created the record Unpublished DI record DI record that has passed GUDID business rules, been Submitted to GUDID AND Publish Date > today (i.e., in the future) Saved indefinitely -- Copy --Unlimited editing --System publishes DI record when Publish Date = today --No -- available for editing by LDE users assigned to the particular Labeler DUNS number --can be viewed by FDA Published DI record DI record that has passed GUDID business rules, been Submitted to GUDID AND Publish Date <= today (i.e., today or in the past) --Cannot move to other DI states without FDA staff intervention Saved indefinitely --Copy --Limited editing during and after Grace Period based on business rules --Yes -- available for editing by LDE users assigned to the particular Labeler DUNS number --can be viewed by Coordinators, LDE users, FDA, Public Users Table 1: Summary of DI Record States 3.2 GUDID Modules Now that the key GUDID concepts are familiar, this section provides a description of the GUDID Modules. The GUDID provides two options for submission of device identification information: 1) Submission of one DI record at a time via the secure GUDID Web Interface. 2) Submission of one DI record per XML file via the HL7 SPL submission option. Both submission options require a GUDID account. Please note that the GUDID account is not by submission type, i.e., a labeler does not need to have a separate GUDID account for each submission option. The GUDID account identifies the labeler in GUDID and enables submission of device information via both options. The overall concepts presented in this guidance document apply to both submission options. Where there are differences, they have been noted. Contains Nonbinding Recommendations 22 GUDID provides two information retrieval options for published DI information: 1) Search and retrieval of device information via the web interface 2) Download and web service capabilities are planned for the future GUDID accounts are NOT required for search and retrieval of published information. During the initial implementation, GUDID Public Search will be temporarily disabled until a meaningful dataset of DI records have been created. Figure 3 provides a pictorial representation of the GUDID modules described above. Figure 3: GUDID Overview 3.2.1 GUDID Web Interface The GUDID Web Interface module enables creation of GUDID accounts, submission of DI records, and search and retrieval of device information. For details related to account creation, see section 3.1.1. This section focuses on submission of device information; search and retrieval details are presented in Section 3.2.3. MZW Typewritten Text GUDID Overview MZW Typewritten Text Contains Nonbinding Recommendations 23 3.2.1.1 GUDID Device Identifier Module The Device Identifier (DI) module enables creation and management of DI records by LDE users. As indicated in Section 3.1.1.2, when coordinators create LDE users, LDE users will receive a temporary login and password via a system generated email. LDE users may then login and use the GUDID. The DI module enables LDE users to: • Create DI records. • Save, edit, and manage Draft DI records. • Review and validate DI records against system business rules. • Copy Unpublished and Published DI records. • Edit and manage Unpublished and Published DI records. • Search and retrieve ALL attributes of DI records for their assigned Labeler DUNS numbers. Note that this is different from public search users who can only view attributes indicated “public” in the Data Elements Reference Table, available on www.fda.gov/udi . The next few sections detail the DI record life-cycle functions in GUDID19. These include: • Creating a New DI Record • Editing a Draft DI Record • Editing Unpublished or Published DI Records • Copying DI Records 3.2.1.1.1 Creation of a New DI Record When created using the GUDID Web Interface, the DI record life-cycle begins with the creation of a new DI record, see Figure 4. Draft DI records cannot be submitted via the HL7 SPL submission option. Once created, a new DI record may be saved as a Draft DI record and Reviewed against the business rules. Based on the Publish Date, the record would then be promoted to the Unpublished or Published DI record state. Figure 4 provides a pictorial representation of the new DI record creation process which is explained below. 19 For detailed information on the accessing and creating DI records in GUDID, please refer to the Global Unique Device Identification Database (GUDID) User Manual, available at -- http://www.fda.gov/downloads/MedicalDevices/DeviceRegulationandGuidance/UniqueDeviceIdentification/GlobalUDIDatabaseGUD ID/UCM396841.pdf http://www.fda.gov/udi Contains Nonbinding Recommendations 24 Figure 4: Creating a New DI Record After creating a new DI record, the LDE user may choose to: • Save the record as Draft DI record. • Cancel creation of a new DI record. • Review DI record to run GUDID business rules o If the record FAILS business rules, the user can:  Save as Draft DI record so errors can be fixed at a later time.  Cancel creation of new DI record. o If the record PASSES business rules, the user can:  Resave as Draft DI record.  Edit record further; once edited, the record must pass business rules again; it can be saved as Draft DI record, or edits can be Cancelled.  Cancel creation of new DI record.  Submit the record to GUDID; the DI record state will be set by the system based on Publish Date.  Unpublished state means Publish Date > today (i.e, a date in the future).  Published state means Publish Date <= today (i.e., today or a date in the past). Note that Submitting a DI record to GUDID does not fulfill your GUDID submission requirements. We will consider you to have complied with the requirements of 21 CFR 830.330 on the date the DI record is saved in the published state. 3.2.1.1.2 Editing a Draft DI Record As noted above, a new DI record created via the GUDID Web Interface can be saved as Draft DI record20, which can move to other DI record states after it passes business rules. Draft DI records can be edited and resaved as Draft DI records. 20 Draft DI records cannot be submitted via the HL7 SPL submission option. Contains Nonbinding Recommendations 25 Figure 5 provides a pictorial representation of editing a Draft DI record, which is explained below. Figure 5: Editing a Draft DI Record The LDE user can edit the Draft DI record and: • Save as Draft again. Recall that Draft DI records can be edited and resaved as drafts an unlimited number of times. o A Draft DI record is purged from the system, i.e., permanently removed from GUDID, after 180 days of inactivity. o Each time a Draft DI record is edited, the 180 calendar day clock is reset as shown in the table below. • Delete the Draft DI record. • Cancel the edits. • Review the Draft DI record to run GUDID business rules. See section 3.2.1.1.1, Creation of New DI Record, for details of the Review process. Contains Nonbinding Recommendations 26 Table 2 below provides an example of how the purge date is reset. Primary DI Number User Action Date User Action Draft DI Record Edit Date Purge Date Comments 100 December 7, 2012 Enter and save a DI record as a draft via the GUDID Web Interface December 7, 2012 June 5, 2013 Draft DI records are saved in the system for 180 calendar days after which the record is purged 100 December 17, 2012 Edit record, resave as draft via the GUDID Web Interface December 17, 2012 June 15, 2013 Purge date is reset each time the record is edited and saved Table 2: Draft DI Purge Date Examples 3.2.1.1.3 Editing Published or Unpublished DI Records A DI record that has passed all business rules, i.e., is Reviewed and Submitted, automatically moves to either the Published or Unpublished DI record state based on the Publish Date, as explained earlier. Published and Unpublished DI records can be edited as follows: • Unpublished DI records can be edited an unlimited number of times and all attributes may be edited; however, once edited, the record must go through Review and pass business rules again. • The extent of editing on a Published DI record is determined by the Grace Period, which starts the day after the DI record is published and ends after 7 calendar days. As explained earlier in the document:  within- the-grace period, all attributes, except Publish Date can be edited.  after-the-grace-period, editing will be limited.  New DI trigger attributes cannot be edited; these are attributes, which when changed, no longer represent the same device and would require a new DI.  Certain attributes will have limited editing capability.  See the GUDID Data Elements Reference Table, available on www.fda.gov/udi , for edit rules for all attributes. Table 3 below illustrates the Grace Period concept via an example. Primary DI Number User/System Action Date User/System Action Publish Date Grace Period Start Date Grace Period End Date Comments 100 July 19, 2013 Create a new DI record, pass business rules; save. July 29, 2013 N/A N/A Unpublished record, grace period does not begin until the record is published http://www.fda.gov/udi Contains Nonbinding Recommendations 27 Primary DI Number User/System Action Date User/System Action Publish Date Grace Period Start Date Grace Period End Date Comments 100 July 23, 2013 Edit record, change publish date July 25, 2013 N/A N/A Unpublished record, grace period does not begin until the record is published 100 July 24, 2013 GUDID nightly system process publishes the record July 25, 2013 July 26, 2013 August 1, 2013, 11:59PM 100 July 27, 2013 Edit New DI trigger attribute within grace period, check that device is combination product July 25, 2013 July 26, 2013 August 1, 2013, 11:59PM Once published, grace period does not reset 100 August 2, 2013 Attempts to edit a New DI trigger attribute, Version or Model Number, but can not July 25, 2013 July 26, 2013 August 1, 2013, 11:59PM New DI trigger attributes CANNOT be edited after grace period ends Table 3: Grace Period Example In addition to editing Draft DI records as explained in Section 3.2.1.1.2, the LDE user can edit Unpublished or Published DI records and: • Review the edited DI record to run GUDID business rules. See Section 3.2.1.1.1 above on Creation of a New DI Record for details of the Review process. • Cancel the edits. Figure 6 provides a pictorial representation of editing an Unpublished or a Published DI record. Contains Nonbinding Recommendations 28 Figure 6: Editing an Unpublished or a Published DI Record There is a key difference between editing a Draft DI record and editing an Unpublished or a Published DI record: • after editing a Draft DI record, it can be resaved as a Draft DI record. • after editing an Unpublished or a Published DI record, the record CANNOT be saved as a Draft DI record; the record has to pass business rules. The record must be Reviewed and Submitted or the edits will be cancelled. All edits to Unpublished and Published DI records are logged in GUDID. LDE users may view the following information about the history of a DI record via the GUDID Web Interface – Edit Date, Edit Time and Name of the user who edited the DI record; for submissions edited via the HL7 SPL submission option, user is noted as “SPL User”. Details of which attributes were edited are presently not exposed and therefore not viewable by users. DI record history information is not exposed to public users of GUDID when a record is retrieved via GUDID Public Search. GUDID offers two DI record submission options, the GUDID Web Interface and the HL7 SPL submission option. Entering a record via one option and editing via another option allows for the possibility of inconsistencies between the labeler’s source data and GUDID data. Therefore, for all edits to a DI record, we recommend you use the same submission option you used to initially create and submit the DI record to GUDID. The labeler is responsible for developing and maintaining SOPs for data quality and data integrity with respect to GUDID submissions. 3.2.1.1.4 Copying DI Records Unpublished and Published DI records can be copied while using the GUDID Web Interface, however Draft DI records cannot. MZW Typewritten Text The figure below illustrates how to edit an unpublished or published DI record MZW Typewritten Text Contains Nonbinding Recommendations 29 • The GUDID Web Interface DI record “Copy” function enables the user to copy all attributes of a DI record to a new DI record, except for the Primary DI number21 and package information. This enables the user to reduce data entry time. • A copied record begins as a Draft DI record and must pass business rules to be promoted to other DI record states. Figure 7 provides a pictorial representation of the Copy functionality in GUDID as explained below. Figure 7: Copying DI Records The LDE user can Copy Unpublished and Published DI records and: • Save as a Draft DI record. Recall that the copied DI record begins as a Draft DI record and follows the DI record life-cycle to move to other DI record states. • Cancel the copy action; the new DI record would not be saved in GUDID. • Review the Copied DI record against GUDID business rules. See Section 3.2.1.1.1 above on Creation of a New DI Record for details of the Review process. 3.2.2 HL7 SPL Submission The HL7 SPL Submission option enables companies to electronically submit device information one DI record at a time as an HL7 SPL xml file via the FDA ESG. For detailed technical specifications on HL7 SPL submission option, please refer to the GUDID HL7 SPL Implementation Files, available at http://www.fda.gov/udi . Companies that choose the HL7 SPL submission option would need to do the following: • Establish a GUDID account. See Section 3.1.1 for details. 21 Primary DI Number is the Device Identifier on the base package of a medical device. http://www.fda.gov/udi MZW Typewritten Text MZW Typewritten Text Copy functionality in GUDID Contains Nonbinding Recommendations 30 o Coordinator and Labeler Data Entry user roles are optional for HL7 SPL submissions since submissions are sent as XML files. However, if labelers choose to have Coordinator and LDE users, they may do so. • Use the FDA ESG to submit HL7 SPL files. o Complete ESG account establishment and testing process. Visit www.fda.gov/esg for more information. • Once GUDID and ESG accounts are established, companies would be required to complete GUDID testing prior to production submissions. Detailed information on testing requirements/process is available as part of the GUDID HL7 SPL Implementation Files on http://www.fda.gov/udi • Companies may choose to use third-party submitters to submit device information on their behalf. Please review Section 3.1.1 for more information on using a third-party to submit device information to GUDID. o We are enabling third-parties to test their GUDID HL7 SPL submission solution by providing them with test GUDID accounts. Labelers using third-parties who may have completed testing must still complete the test scenarios listed as part of the GUDID HL7 SPL Implementation Files prior to moving to production GUDID HL7 SPL submissions. 3.2.3 Search/Retrieval of Device Information The GUDID Search and Retrieval module would enable public users, i.e., consumers, health-care providers, hospital systems, to access published GUDID data. Published data would include all DI record attributes with a few exceptions such as: Labeler DUNS Number, Company Physical Address, GMDN Preferred Term Code, FDA Listing Number, etc. Please see the GUDID Data Elements Reference Table, available on www.fda.gov/udi for a list of attributes that are not released to the public. During the initial implementation, GUDID Public Search will be temporarily disabled until a meaningful dataset of DI records have been created. As indicated earlier, there would be two Search and Retrieval options available in GUDID: • Search and retrieval of device information via the Web Interface • System to system search and retrieval Please note that GUDID accounts are not necessary for search or retrieval of published information. 3.2.3.1 GUDID Web Interface Search and Retrieval The GUDID Web Interface search and retrieval module would provide the ability to: • Search published GUDID data • View results • Export results as xml files Two search options are available via the GUDID Web Interface: • Quick Search – allows search on the following attributes: Device Identifier, Company Name, Brand Name, GMDN Preferred Term Name and Model Number. • Advanced Search – allows search on additional GUDID attributes. http://www.fda.gov/esg http://www.fda.gov/udi http://www.fda.gov/udi Contains Nonbinding Recommendations 31 3.2.3.2 GUDID System to System Search and Retrieval We plan to make available all published GUDID data as download files. Additionally, we also plan to make available basic web service functionality. Additional information on both these capabilities will be provided on the UDI webpage when available. 4 GUDID Submissions and 21 CFR 11 Requirements There are two requirements necessary for Part 11 applicability: 1) Records that are required to be maintained (under predicate rules) or submitted to FDA 2) Records that are kept in electronic format, as opposed to paper Labelers should become familiar with all the requirements of 21 CFR 11 and the Guidance document (Part 11 Electronic Records; Electronic Signatures – Scope and Application, which can be found at: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm125125.pdf) which further defines a narrowed scope and identifies the requirements for which compliance is most important while Part 11 is being re-examined. When reading the Guidance document, ‘predicate rule’ should be interpreted as 78 FR 58786 or the UDI Rule. All submitters – must retain records in accordance with 21 CFR 830.360. If those records are kept electronically, part 11 applies. However, a record that is not itself submitted, but is used in generating a submission, is not a part 11 record. That is, a record developed to collect all the data elements required to be entered into a device record via the GUDID web user interface, is not subject to part 11 requirements. SPL submitters – must retain records in accordance with 21 CFR 830.360 and all records submitted to FDA. The HL7 SPL solution must be compliant with the requirements of part 11. The GUDID SPL submission doesn’t require a signature; therefore, part 11 requirements specific to electronic signatures (21 CFR 11 Subpart C), do not apply. However, please don’t confuse an electronic signature with a digital certificate. A digital certificate serves to authenticate the sender and is required for all submissions to the FDA ESG, including GUDID. Once an SPL submission is successfully delivered to the GUDID, labelers should be able to view and edit data elements via the web interface. This allows for the possibility of inconsistencies between the labeler’s source data submitted via SPL and GUDID data. Labelers should develop and adhere to SOPs for data governance to maintain the quality of their device data. Third-party submitters/Solutions Providers – are not responsible to the FDA to meet regulatory requirements for UDI or part 11. It is the legal responsibility of the labeler (or data owner) to meet the records requirements for 21 CFR 830.360 and the requirements of 21 CFR 11. The contractual language between labeler and third- party submitter is not the purview of the FDA. 5 Conclusion This document provides GUDID information based on the current implemented system version. Enhancements and upgrades to GUDID are anticipated and the FDA intends to periodically update this document to reflect system changes. http://www.fda.gov/downloads/RegulatoryInformation/Guidances/ucm125125.pdf Contains Nonbinding Recommendations 32 Appendix A – GUDID Package Information Examples22 The examples below illustrate how package information is entered into the GUDID along with attribute values pertinent to packages. EXAMPLE 1: UNIT OF USE DI + ONE PACKAGE LEVEL The figure below provides a package configuration example for GUDID where the medical device has Unit of Use DI Number and one package level. • Box of 100 single use blood collection tubes with the Primary DI 20001 and Device Count = 100. o Note that the tubes themselves do not have the DI on them as they fall under the general exception for individual single use device under 801.30(a)(3). Each tube however, gets a virtual Unit of Use DI assigned, and in this case, 10001. • Case of 8 boxes (800 total), with Package DI 30001 (contains 8 of Primary DI 20001), Quantity per Package = 8. • Package Discontinue Date is blank, therefore system auto-populates Package Status to “In Commercial Distribution.” Package 30001 inherits all attribute values of base package 20001, except for the attributes specific to 30001 such as Quantity per Package, as shown in the table below. Base Package Primary Device Identifier Device Count Unit of Use DI 20001 100 10001 Package DI Package DI Quantity per Package Contains DI Package Package Type Package Discontinue Date Package Status 30001 8 20001 Case In Commercial Distribution 22 Device Identifiers used in all the examples are fictitious. Please refer to “UDI Formats by FDA Accredited Issuing Agency” (see Appendix C, available on www.fda.gov/udi ) for correct format of the DI numbers by FDA Accredited Issuing Agencies. http://www.fda.gov/udi MZW Typewritten Text Quantity per package Contains Nonbinding Recommendations 33 Figure 1: GUDID Package Configuration Example 1 Contains Nonbinding Recommendations 34 EXAMPLE 2: DI ON INDIVIDUAL DEVICE + MULTIPLE PACKAGE LEVELS The figure below provides a package configuration example for GUDID where the DI is on the individual device with two package levels. • Catheter, 12 Fr, each with Primary DI 1001 and Device Count = 1. • Box of 30 catheters with Package DI 2001 (contains 30 of Primary DI 1001). • Case of 12 boxes (540 catheters), with Package DI 3001 (contains 12 of Package DI 2001). • Box of 50 catheters with Package DI 2002 (contains 50 of Primary DI 1001). • Package Discontinue Date is blank, therefore system auto-populates Package Status to “In Commercial Distribution.” Package 2001, 3001 and 2002 inherit all attribute values of base package 1001, except for the attributes specific to each package, as shown in the table below. Base Package Primary Device Identifier Device Count 1001 1 Package DI Package DI Quantity per Package Contains DI Package Package Type Package Discontinue Date Package Status 2001 30 1001 Box In Commercial Distribution 3001 12 2001 Case In Commercial Distribution 2002 50 1001 Box In Commercial Distribution MZW Typewritten Text Package Configurations of the Base Package MZW Typewritten Text Contains Nonbinding Recommendations 35 Figure 2: Package Configuration Example 2 Contains Nonbinding Recommendations 36 Appendix B – GUDID Data Elements Reference Table For a complete list of GUDID attributes, please refer to the GUDID Data Elements Reference Table available at www.fda.gov/udi http://www.fda.gov/udi Contains Nonbinding Recommendations 37 Appendix C – UDI Formats by FDA Accredited Issuing Agency For information on UDI Formats by FDA Accredited Issuing Agency, please visit www.fda.gov/udi http://www.fda.gov/udi Contains Nonbinding Recommendations 38 Appendix D – GUDID Attributes Mapped to a Fictitious Medical Device Label Many GUDID data attributes appear on the medical device label. When a GUDID attribute appears on the medical device package/label, the values submitted to the GUDID should match the value on the label. Figure D1 shows a fictitious medical device label and identifies the GUDID data attributes that appear on the label. Figure D1: GUDID Attributes Mapped to a Fictitious Medical Device Label NOTE: Representation of GMDN above is for illustration purposes ONLY. GMDN PT Name and Definition are NOT expected to appear on the label of a device. MZW Typewritten Text Sample Device Labeling MZW Typewritten Text Contains Nonbinding Recommendations 39 Abbreviations & Acronyms Term Description DI Device Identifier D&B Dun & Bradstreet DUNS Data Universal Numbering System ESG FDA Electronic Submissions Gateway GMDN Global Medical Device Nomenclature GUDID Global Unique Device Identification Database HCT/P Human Cell, Tissue or Cellular or Tissue-Based Product FDA Food and Drug Administration FDAAA FDA Amendments Act FDASIA FDA Safety and Innovation Act HL7 Health Level 7 PI Production Identifier GMDN PT GMDN Preferred Term SPL Structured Product Labeling UDI Unique Device Identifier Contains Nonbinding Recommendations 40 Glossary Term Description Base Package The lowest level of a medical device package containing a full UDI. The DI on the base package is the Primary DI. Coordinator Individual(s) responsible for management of the GUDID account, for designated Labelers. Data Universal Numbering System (DUNS) A unique 9-digit identification number assigned and managed by Dun & Bradstreet to business entities. Device Identifier (DI) A mandatory, fixed portion of a UDI that identifies the labeler and the specific version or model of a device. Device Identifier Record (DI Record) The DI, together with associated data attributes constitutes a DI record for a particular device version or model. DI Record Life-Cycle Comprises of the various states of a DI record and the associated business rules and functionality available to a user. DI Record States A DI Record is in one of three DI Record States at any given time: Draft DI Record, Unpublished DI Record, or Published DI Record. Direct Marking DI An identifier that is marked directly on the device; can be the same as or different from the Primary DI; only applicable to devices subject to Direct Marking requirements under 21 CFR 801.45. Device Package A package that contains a fixed quantity of a particular version or model of a device. Draft DI Record Saved DI record that has not passed business rules. Electronic Submissions Gateway (ESG) An FDA-wide solution for accepting secure electronic regulatory submissions. FDA Preferred Term The FDA Preferred Term (PT) Codes are a 4-letter code assigned to each GMDN term, in place of the GMDN Code. FDA PT Codes only apply to GUDID DI Record entry ONLY and cannot be used in place of GMDN Codes for any other system. Global Medical Device Nomenclature (GMDN) A system of internationally agreed descriptors used to identify medical device products and is managed by the GMDN Agency. Grace Period Seven calendar days and starts the day after the DI record is published; determines the extent of editing possible on a DI record. GUDID Global Unique Device Identification Database, the repository of device identification information for devices specified under the FDA UDI Final Rule. GUDID Account A GUDID account enables companies to access and submit information to the GUDID. Contains Nonbinding Recommendations 41 Term Description GUDID Web Interface An online interface that enables secure account creation, secure submission of DI records, and search and retrieval of device information. Health Level 7 (HL7) A standards development organization, whose mission is to provide messaging standards for interoperability, exchange, management, and integration of data that supports clinical patient care and the management, delivery, and evaluation of healthcare services. Issuing Agency Organization accredited by FDA to operate a system for the issuance of UDIs. Labeler Any person who causes a label to be applied to a device with the intent that the device will be commercially distributed without any intended subsequent replacement or modification of the label; and, any person who causes the label of a device to be replaced or modified with the intent that the device will be commercially distributed without any subsequent replacement or modification of the label, except that the addition of the name of, and contact information for, a person who distributes the device, without making any other changes to the label, is not a modification for the purposes of determining whether a person is a labeler. Labeler Data Entry (LDE) User Individual(s) responsible for day to day entry, submission and management of device identification information for designated Labeler DUNS into the GUDID. Listing Number Number assigned by FDA during Registration and Listing to all devices in commercial distribution, regardless of pre-market authorization requirements per 21 CFR 807.28(f) New DI Trigger Attributes Attributes, which when changed, no longer represent the same device thereby requiring the creation of a new DI. Package According to 21 CFR 801.3, a package is defined as a fixed quantity of a particular version or model of a device. Package DI A device identifier for the package configuration that contains multiple units of the base package (does not include shipping containers). Primary DI An identifier that is the main (primary) lookup for a medical device and meets the requirements to uniquely identify a device through its distribution and use. The Primary DI would be located on the base package, which is the lowest level of a medical device containing a full UDI. For medical devices without packaging, the Primary DI number and full UDI may be on the device itself. Product Code Three letter classification code for pre-market devices issues by FDA. Contains Nonbinding Recommendations 42 Term Description Production Identifier(s) (PI) A conditional, variable portion of a UDI that identifies one or more of the following when included on the label of the device: (i) The lot or batch within which a device was manufactured; (ii) The serial number of a specific device; (3) The expiration date of a specific device; (iv) The date a specific device was manufactured. (v) For an HCT/P regulated as a device, the distinct identification code required by § 1271.290(c). Published DI Record A DI record that is published, and therefore is available for search and retrieval by the public. Regulatory Contact Individual responsible for management of GUDID submission requirements for the Labelers in a given GUDID account. Relabler Relabeler, for the purposes of 21 CFR 830.60, is a new labeler that changes the content of the labeling from that supplied from the original labeler for distribution under the new labeler's own name. A relabeler does not include labelers that do not change the original labeling but merely add their own name. Secondary DI An identifier that is an alternate (secondary) lookup for a medical device that is issued from a different issuing agency than the primary DI. Structured Product Labeling (SPL) A HL7 standard for the exchange of product information using extensible markup language. Support Contact Contact for consumers and healthcare providers to obtain additional information about the device. Third-party submitters Companies/individuals (contractors, vendors) authorized to submit GUDID information on behalf of the Labeler. Unique Device Identifier (UDI) A unique numeric identifier composed of the device identifier and production identifier(s) that uniquely identify a medical device through distribution and use. Unit of Use DI An identifier assigned to an individual medical device when a UDI is not labeled on the individual device at the level of its unit of use. Its purpose is to associate the use of a device to/on a patient. Unpublished DI Record DI record that has passed GUDID business rules AND Publish Date > today. 1 Introduction 2 Unique Device Identifier (UDI) 3.1 GUDID Key Concepts 3.1.1 GUDID Account 3.1.1.1 Preparatory Steps Prior to Requesting a GUDID Account 3.1.1.2 GUDID Account Request Process 3.1.1.3 GUDID Account Changes 3.1.2 Device Identifier (DI) Record 3.1.2.1 Package Information in GUDID 3.1.2.2 Global Medical Device Nomenclature (GMDN) 3.1.3 DI Record Life-Cycle 3.1.3.1 DI Record States 3.2 GUDID Modules 3.2.1 GUDID Web Interface 3.2.1.1 GUDID Device Identifier Module 3.2.1.1.1 Creation of a New DI Record 3.2.1.1.2 Editing a Draft DI Record 3.2.1.1.3 Editing Published or Unpublished DI Records 3.2.1.1.4 Copying DI Records 3.2.2 HL7 SPL Submission 3.2.3 Search/Retrieval of Device Information 3.2.3.1 GUDID Web Interface Search and Retrieval 3.2.3.2 GUDID System to System Search and Retrieval 4 GUDID Submissions and 21 CFR 11 Requirements 5 Conclusion Appendix A – GUDID Package Information Examples21F Example 1: Unit of Use DI + One Package Level Example 2: DI on Individual Device + Multiple Package Levels Appendix B – GUDID Data Elements Reference Table Appendix C – UDI Formats by FDA Accredited Issuing Agency Appendix D – GUDID Attributes Mapped to a Fictitious Medical Device Label Abbreviations & Acronyms

Bundesministerium für Gesundheit Bekanntmachung eines Beschlusses des Gemeinsamen Bundesausschusses über die Einstellung der Nutzenbewertung von Arzneimitteln im Bestandsmarkt Vom 17. April 2014 Der Gemeinsame Bundesausschuss hat in seiner Sitzung am 17. April 2014 Folgen- des beschlossen: Nach Aufhebung des § 35a Absatz 6 des Fünften Buches Sozialgesetzbuch (SGB V) durch Inkrafttreten von Artikel 1 Nummer 1 des 14. SGB V-Änderungsgesetzes vom 27. März 2014 (BGBl. I S. 261) werden 1. die mit Beschluss vom 18. April 2013 und 14. November 2013 veranlassten Nut- zenbewertungen von Arzneimitteln mit neuen Wirkstoffen im Bestandsmarkt und 2. die zum 1. September 2013 eingeleitete Nutzenbewertung des Wirkstoffs Saxa- gliptin für ein neues Anwendungsgebiet eingestellt. Die Tragenden Gründe zu diesem Beschluss werden auf den Internetseiten des Gemeinsamen Bundesausschusses unter www.g-ba.de veröffentlicht. Berlin, den 17. April 2014 Gemeinsamer Bundesausschuss gemäß § 91 SGB V Der Vorsitzende Hecken www.bundesanzeiger.de Bekanntmachung Veröffentlicht am Mittwoch, 14. Mai 2014 BAnz AT 14.05.2014 B2 Seite 1 von 1

Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung Informationsveranstaltung des BAH Berlin, 23. Mai 2013 Thomas Müller Arzt und Apotheker, Leiter Abteilung Arzneimittel des Gemeinsamen Bundesausschusses Seite 3 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Nutzenbewertung Bestandsmarkt Für bereits zugelassene und im Verkehr befindliche Arzneimittel kann der G-BA eine Nutzenbewertung nach §35a SGB V veranlassen. Vorrangig zu bewerten sind: - Arzneimittel, die für die Versorgung von Bedeutung sind; - Arzneimittel, die mit Arzneimitteln im Wettbewerb stehen, für die ein Beschluss nach der frühen Nutzenbewertung nach § 35a SGB V vorliegt. Vor Aufforderung aus dem Bestandsmarkt muss der G-BA eine Beratung anbieten. Der pharmazeutische Unternehmer übermittelt dem G-BA die Nachweise (Dossier) innerhalb von drei Monaten. Seite 4 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Geltungsbereich der Bestandsmarktnutzenbewertung Erstattungsfähige Arzneimittel mit neuen Wirkstoffen im Sinne des 5. Kapitel § 2 Abs. 1 VerfO  Erstmalig vor dem 1. Januar 2011 in den Verkehr gebracht  Bestehender Unterlagenschutz bei Inkrafttreten des verhandelten Erstattungsbetrags nach §130b SGB V Nicht aufgerufen werden Wirkstoffe mit Arzneimitteln, die  Vom G-BA als zweckmäßige Vergleichstherapie bestimmt wurden  Der Festbetragsregelung unterliegen  Von der Verordnung ausgeschlossen sind Seite 5 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Aufruf der Gliptine aus dem Bestandsmarkt (1) Mit Beschluss vom 07.06.2012 aufgerufen zur Nutzenbewertung:  Sitagliptin, Sitagliptin/Metformin  Vildagliptin, Vildagliptin/Metformin  Saxagliptin Von Bedeutung für die Versorgung und im Wettbewerb mit Linagliptin. Im Wettbewerbsverhältnis, da zur Behandlung des gleichen Patientenkreises, sowie pharmakologisch vergleichbar (Dipeptidyl- Peptidase-Inhibitoren, Gliptine). Die Dossiers waren bis spätestens zum 31.12.2012 vorzulegen. … Seite 6 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Aufruf der Gliptine aus dem Bestandsmarkt (2) Zwischenverfügung vom 20.12.2012 des Landessozialgerichts Berlin- Brandenburg im Rahmen eines einstweiligen Rechtsschutzverfahrens (Az.: L 7 KA 106/12 KL ER) : Frist zur Dossiervorlage für den Wirkstoff Vildagliptin verlängert bis zum 31.03.2013 Mit G-BA-Beschluss vom 17.01.2013 zur Vermeidung von Wettbewerbsverzerrungen auch Fristverlängerung für Sitagliptin und Saxagliptin zum 31.03.2013. LSG Berlin-Brandenberg lehnt am 28.02.2013 den Eilantrag im einstweiligen Rechtschutzverfahren ab. LSG Berlin-Brandenburg entscheidet am 15.05.2013 im Hauptsacheverfahren und weist Klagen als unzulässig ab. Seite 7 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Aufruf der Gliptine aus dem Bestandsmarkt (3) Gesetzentwurf Drittes Gesetz zur Änderung arzneimittelrechtlicher und anderer Vorschriften Vorgeschlagene Änderung SGB V§35a und AM-NutzenV Klarstellung, „da in der Rechtssprechung Zweifel auftraten, ob diese geetzliche Verweiskette hinreichend bestimmt ist, um insbesondere die Rechtsbehelfsregelung des Absatzes 8 auch auf den Bestandsmarktaufruf nach Absatz 6 anwenden zu können“ “Die Erwartung, dass der Bestandsmarkt in der Zukunft dauerhaft ausgespart bleibt, wird gesetzlich nicht geschützt.” Seite 8 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Operationalisierung der Kriterien zum Bestandsmarktaufruf Gesetzliche Anforderung „für die Versorgung von Bedeutung“ wird operationalisiert durch  das wirtschaftliche Gewicht (Umsatz) eines Arzneimittels im GKV- Arzneimittelmarkt,  die verordnete Menge an Packungen als Ausdruck für die Zahl der damit versorgten Patienten.  Keine Momentaufnahme sondern Potentialbetrachtung für nachhaltige Wirkung  Damit wird ein willkürfreies, nachvollziehbares, vorhersehbares und transparentes Aufgreifmodell geschaffen, das damit auch ein hohes Mass an Rechtssicherheit besitzt Seite 9 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Ermittlung des Potenzials Prinzip einer Vorausberechnung:  Bestimmung des Status im „Produktlebenszyklus“  Berechnung des aktuellen Umsatzes und aktueller Verordnungszahlen (auf Grundlage der letzten 12 Kalendermonate)  Anschließend Prognose anhand typisierter Umsatz- und Verordnungs- entwicklungen1 für die Restlaufzeit des Unterlagenschutzes 1 auf der Basis von 188 Wirkstoffen (vgl. Arzneimittelverordnungsreport 2012) Seite 10 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Typisierter Umsatzverlauf und Wachstumsrate Seite 11 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Typisierter Verordnungsverlauf und Wachstumsrate -50% 0% 50% 100% 150% 200% 250% 0 100 200 300 400 500 600 700 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Verordnungen in Tsd. je Patent Wachstumsrate Verordnung Seite 12 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Mechanismus der Vorausberechnung Seite 13 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Rangfolge der Wirkstoffe  Getrennte Rangbildung nach  prognostischem Umsatz („Umsatzrang“)  prognostischer Verordnungszahl („Verordnungsrang“)  Anschließend Gesamtrangbildung aus Umsatzrang und Verordnungsrang  Wichtung des Umsatzrangs: 80 v. H.  Wichtung des Verordnungsrangs: 20 v. H.  Gewichteter Gesamtrang Seite 14 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Initialwirkstoffe und versorgungsrelevante Anwendungsgebiete  Gewichteter Gesamtrang bestimmt aufzurufende Initialwirkstoffe aus dem Bestandsmarkt  Initialwirkstoffe stehen stellvertretend für für die Versorgung relevante Anwendungsgebiete  Identifikation weiterer Wirkstoffe mit relevantem Anwendungsgebiet und Aufruf dieser Wirkstoffe Initialwirkstoff Anwendungs- gebiet A Anwendungs- gebiet B Wirkstoff Anwendungs- gebiet C Wirkstoff Wirkstoff Wirkstoff Wirkstoff Wirkstoff Seite 15 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Ergebnisse des ersten Aufrufs (1) Wirkstoff Anwendungsgebiet Zeitpunkt zur Dossiervorlage 1 Tapentadol* Starke, chronische Schmerzen 15.10.2013 2 Denosumab* Osteoporose; Knochenmetastasen 15.10.2013 Ranelicsäure, Distrontiumsalz Osteoporose 15.10.2013 Parathyroidhormon, rekombiniert Osteoporose 15.10.2013 Teriparatid Osteoporose 15.10.2013 3 Rivaroxaban* Vorhofflimmern, Prophylaxe Schlaganfall und kardioembolische Erkrankungen; tiefe Venenthrombose 01.12.2013 Dabigatran Vorhofflimmern, Prophylaxe Schlaganfall und kardioembolische Erkrankungen; tiefe Venenthrombose 01.12.2013 * Initialwirkstoffe Seite 16 | 23. Mai 2013 | Die neuen G-BA-(Verfahrens-)Regeln zum Aufruf des Bestandsmarktes zur Nutzenbewertung © 2013, Thomas Müller Ergebnisse des ersten Aufrufs (2) Wirkstoff Anwendungsgebiet Zeitpunkt zur Dossiervorlage 4 Liraglutid* Diabetes mellitus Typ 2 01.01.2014 Exenatid Diabetes mellitus Typ 2 01.01.2014 5 Agomelatin* Depression 01.02.2014 Duloxetin Depression; Schmerzen, bei diabetischer Polyneuropathie; Dranginkontinenz Frauen 01.02.2014 6 Tocilizumab* Rheumatoide Arthritis 01.03.2014 Golimumab Rheumatoide Arthritis; Arthritis psoriatica; Ankylosierende Spondylitis 01.03.2014 Certolizumab pegol Rheumatoide Arthritis 01.03.2014 * Initialwirkstoffe

Das UDI-System soll in der EU eingeführt werden, um die Sicherheit von Medizinprodukten zu erhöhen und den Patientenschutz zu verbessern. Gleichzeitig soll eine Basis für eine globale Medizinprodukte-Überwachung geschaffen werden. Der Schutz vor Fälschungen ist hierbei lediglich ein sekundäres Ziel. Mit UDI soll ein einheitliches maschinenlesbares Kennzeichen zusätzlich zu den bereits bestehenden Kennzeichnungspflichten für Medizinprodukte eingeführt werden. Bei einer Verwirklichung würde die Nutzung von Auto-ID-Technologien für Medizinprodukte rechtsverbindlich werden. Das UDI-Konzept setzt sich zusammen aus einem eindeutigen Identifikationscode basierend auf global akzeptierten Standards sowie einer UDI-Datenbank. „Unique“ bedeutet allerdings nicht die Serialisierung, also die individuelle Kennzeichnung jedes einzelnen Medizinprodukts, sondern eine einheitlich standardisierte Produktidentifikation. In der Sitzung am 17. Januar 2011 wurden die Grundlagen für eine mögliche Einführung von UDI auf europäischer Ebene erörtert. Die Aktivitäten der EU-Kommission sind kein Alleingang, sondern basieren auf bereits bestehenden Ideen der US-amerikanischen FDA und auch der GHTF (Global Harmonization Task Force), die bereits in entsprechenden Arbeitsgruppen erhebliche Fortschritte erzielt haben. So hat die GHTF am 04. November 2010 ihren Entwurf eines UDI-Systems veröffentlicht. Dieses Dokument stellte die Basis der Diskussionen der Working Group dar.

Das IMDRF ist eine Nachfolgeinitiative der GHTF und setzt sich aus Behördenvertretern von Australien, Brasilien, Kanada, China, Europa, Japan und den USA zusammen. Erklärtes Ziel ist es, auf internationaler Ebene eine regulatorische Harmonisierung und Konvergenz bei Medizinprodukten zu erreichen. Das nun veröffentlichte Papier geht auf ein Dokument der GHTF vom September 2011 zurück. Ein global einheitliches Vorgehen bei UDI soll länderspezifische Anforderungen in Bezug auf die Kernelemente des UDI-System vermeiden. Auch wenn das Dokument nicht verbindlich ist, ist zu erwarten, dass die Regulierungsbehörden der beteiligten Länder / Regionen bei der Entwicklung ihrer eigenen Anforderungen dem Rahmen folgen. Laut Artikel 24 des Kommissionsvorschlags zur Europäischen Medizinprodukte-Verordnung (MDR) sollen die UDI Anforderungen an bestimmte Kategorien oder Produktgruppen mittels delegierter Rechtsakte festgesetzt werden. Seitens der Europäischen Kommission liegt außerdem eine Empfehlung für UDI vor (vgl. BAH Schreiben vom 11. April 2013), die u.a. einen „der Klassifizierung des Produkts angemessenen risikobasierten Ansatz“ fordert. Bemerkenswert ist u.a. die Tatsache, dass der IMDRF-Entwurf der Leitlinie die Anforderungen für nicht-verschreibungspflichtige Medizinprodukte einschränkt: „Non-prescription medical devices exclusively for retail Point of Sale (POS) do not need to 436 encode Production Identifiers in AIDC on the point of sale package.“ (Kapitel 8, Nr. 3) Insgesamt gibt es also Ansätze auf internationaler und europäischer Ebene, die UDI-Anforderungen für bestimmte Medizinprodukte (Klasse I/IIa) einzuschränken. Entsprechende Änderungsanträge (ENVI 443 und 444) in Bezug auf den ENVI-Berichtsentwurf wurden ebenfalls von EU-Parlamentariern eingebracht und werden vom BAH unterstützt (vgl. oben). Der IMDRF-Leitfaden soll bis 14. November 2013 im Rahmen des nächsten IMDRF-Meetings in Brüssel finalisiert werden.

Beschluss des Gemeinsamen Bundesausschusses über eine Änderung der Arzneimittel-Richtlinie (AM-RL): Anlage XII - Beschlüsse über die Nutzenbewertung von Arzneimitteln mit neuen Wirkstoffen nach § 35a SGB V – Sofosbuvir Vom 17. Juli 2014 Der Gemeinsame Bundesausschuss hat in seiner Sitzung am 17. Juli 2014 beschlossen, die Richtlinie über die Verordnung von Arzneimitteln in der vertragsärztlichen Versorgung (Arzneimittel-Richtlinie) in der Fassung vom 18. Dezember 2008 / 22. Januar 2009 (BAnz. Nr. 49a vom 31. März 2009), zuletzt geändert am TT. MM JJJJ (BAnz AT TT. MM JJJJ Bx), wie folgt zu ändern: I. Die Anlage XII wird in alphabetischer Reihenfolge um den Wirkstoff Sofosbuvir wie folgt ergänzt: 2 Sofosbuvir Beschluss vom: 17. Juli 2014 In Kraft getreten am: 17. Juli 2014 BAnz AT TT. MM JJJJ Bx Zugelassenes Anwendungsgebiet: Sofosbuvir (Sovaldi®) wird in Kombination mit anderen Arzneimitteln zur Behandlung der chronischen Hepatitis C (CHC) bei Erwachsenen angewendet (siehe Abschnitte 4.2, 4.4 und 5.1 der Fachinformation von Sovaldi®). Zur spezifischen Aktivität gegen die verschiedenen Genotypen des Hepatitis-C-Virus (HCV) siehe Abschnitte 4.4 und 5.1. der Fachinformation von Sovaldi®). 1. Zusatznutzen des Arzneimittels im Verhältnis zur zweckmäßigen Vergleichstherapie a) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin + Proteaseinhibitor (Boceprevir oder Telaprevir) bei therapienaiven Patienten ohne Zirrhose mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) oder Triple-Therapie (Kombination aus einem Proteaseinhibitor (Boceprevir oder Telaprevir), Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin + Proteaseinhibitor (Boceprevir oder Telaprevir): Anhaltspunkt für einen geringen Zusatznutzen. Studienergebnisse nach Endpunkten (NEUTRINO)1 Endpunkt Interventionsgruppe SOF+ RBV+PEG (N = 327 Gesamtpopulation) Patient mit Ereignissen n (%) Mortalität Gesamtmortalität 0 (0) 1 Daten zu HCV-Patienten, aus dem Assessment report zu Sovaldi (Procedure No. EMA/H/C/002798/0000), Tabelle 8, Tabelle 17, Tabelle 18; NEUTRINO-Studie (Phase III, multizentrisch, einarmig, therapienaive HCV Patienten mit den Genotypen 1, 4, 5 oder 6; Therapieregime Sofosbuvir plus Ribavirin plus PegInterferon über 12 Wochen). 3 Morbidität SVR 122 Responder Teilpopulation Genotyp 1 (N = 292) 262 (89,7) Teilpopulation Genotyp 1, 4, 5, 6 (ohne Zirrhose) (N = 273) 253 (92,7) Gesundheitsbezogene Lebensqualität Keine Angabe von Daten Nebenwirkungen (Gesamtpopulation) UE 310 (94,8) SUE 4 (1,2) Abbruch wegen UE 8 (2,4) Systemorganklasse aus MedDRA; Preferred Term Allgemeine Erkrankungen und Beschwerden am Verabreichungsort Fatigue 192 (58,7) Grippeähnliche Erkrankungen 51 (15,6) Husten 34 (10,4) Fieber 58 (17,7) Reizbarkeit 42 (12,8) Schmerz 33 (10,1) Schüttelfrost 54 (16,5) Dyspnoe 39 (11,9) Erkrankungen des Nervensystems Kopfschmerzerkrankungen 118 (36,1) Schwindelgefühl 41 (12,5) Erkrankungen des Blutes und des Lymphsystems Anämie 68 (20,8) Neutropenie 54 (16,5) Erkrankungen des Gastrointestinaltrakts Diarrhoe 38 (11,6) Übelkeit 112 (34,3) Erbrechen 39 (11,9) Psychiatrische Erkrankungen Depression 31 (9,5) Schlaflosigkeit 81 (24,8) 2 SVR 12: Dauerhaftes virologisches Ansprechen, 12 Wochen nach Therapieende. 4 Erkrankungen der Haut und des Unterhautzellgewebes Ausschlag 59 (18,0) Pruritus 54 (16,5) Stoffwechsel und Ernährungsstörungen Appetit vermindert 58 (17,7) Skelettmuskulatur-, Bindegewebs- und Knochenerkrankungen Arthralgie 47 (14,4) Myalgie 45 (13,8) b) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven Patienten mit Zirrhose mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin: Anhaltspunkt für einen geringen Zusatznutzen. Studienergebnisse nach Endpunkten (NEUTRINO)1 Endpunkt Interventionsgruppe SOF+ RBV+PEG (N = 327 Gesamtpopulation) Patient mit Ereignissen n (%) Mortalität Gesamtmortalität 0 (0) Morbidität SVR 122 Responder Teilpopulation Genotyp 1 (N = 292) 262 (89,7) Teilpopulation Genotyp 1,4,5,6 (mit Zirrhose) (N = 54) 43 (79,6) Gesundheitsbezogene Lebensqualität Keine Angabe von Daten Nebenwirkungen (Gesamtpopulation) Die Daten sind für die Gesamtpopulation bereits unter a) „In Kombination mit PegInterferon + Ribavirin gegenüber PegInterferon + Ribavirin + Proteaseinhibitor (Boceprevir oder Telaprevir) bei therapienaiven Patienten ohne Zirrhose mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1)“ abgebildet. Daten für die jeweiligen Teilpopulationen liegen nicht vor. 5 c) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin + Proteaseinhibitor (Boceprevir oder Telaprevir) therapieerfahrenen Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) oder Triple-Therapie (Kombination aus einem Proteaseinhibitor (Boceprevir oder Telaprevir), Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin + Proteaseinhibitor (Boceprevir oder Telaprevir): Ein Zusatznutzen ist nicht belegt. d) In Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 2) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin: Hinweis für einen beträchtlichen Zusatznutzen. Studienergebnisse nach Endpunkten (FISSION)3: Endpunkt Interventionsgruppe SOF+ RBV (N = 70 Genotyp 2) Kontrollgruppe PEG + RBV (N = 67 Genotyp 2) Intervention vs. Kontrolle Patient mit Ereignissen n (%) Patient mit Ereignissen n (%) RR [95% -KI] p-Wert Mortalität Gesamtmortalität 0 (0) 0 (0) - Morbidität SVR 244 Responder 68 (97,1) 51 (76,1) 1,28 [1,11; 1,47]; < 0,001 Gesundheitsbezogene Lebensqualität SF 36 Keine verwertbaren Daten für die Teilpopulation Genotyp 2 (therapienaiv). 3 Daten zu HCV-Patienten, Genotyp 2 (therapienaiv) aus der Nutzenbewertung Sofosbuvir (A 14-05) des IQWiG; Tabelle 14. 4 Dauerhaftes virologisches Ansprechen, 24 Wochen nach Therapieende. 6 Nebenwirkungen5 UE 60 (85,7) 61 (91,0) - SUE 1 (1,4) 1 (1,5) - Abbruch wegen UE 0 (0) 8 (11,9) - Weitere Daten zu Nebenwirkungen aus der FISSION-Studie6 Endpunkt Interventionsgruppe SOF+ RBV (N=256 Gesamtpopulation) Kontrollgruppe PEG + RBV (N=243 Gesamtpopulation) Systemorganklasse aus MedDRA; Preferred Term Patient mit Ereignissen n (%) Patient mit Ereignissen n (%) Gesamtrate 220 (85,9) 233 (95,9) Allgemeine Erkrankungen und Beschwerden am Verabreichungsort Fatigue 92 (35,9) 134 (55,1) Fieber 6 (2,3) 33 (13,6) Grippeähnliche Erkrankungen 7 (2,7) 44 (18,1) Reizbarkeit 25 (9,8) 40 (16,5) Schmerz 5 (2,0) 30 (12,3) Schüttelfrost 7 (2,7) 43 (17,7) Erkrankungen des Nervensystems Kopfschmerzerkrankungen 64 (25,0) 108 (44,4) Schwindelgefühl 27 (10,5) 33 (13,6) Erkrankungen des Blutes und des Lymphsystems Anämie 20 (7,8) 28 (11,5) Neutropenie 0 (0) 30 (12,3) Erkrankungen des Gastrointestinaltrakts Diarrhoe 23 (9,0) 42 (17,3) Übelkeit 46 (18,0) 70 (28,8) Psychiatrische Erkrankungen Depression 14 (5,5) 34 (14,0) 5 Insbesondere wegen des großen Unterschiedes in der Beobachtungsdauer zwischen den Behandlungsarmen (Interventionsarm: 12 Wochen; Vergleichsarm: 24 Wochen) sind die Ergebnisse zu den Nebenwirkungen nur qualitativ interpretierbar. Bei dem Endpunkt „Abbruch wegen UE“ handelt es sich zudem um einen subjektiven Endpunkt aus einer offenen Studie. In der Gesamtrate UE sind auch nicht patientenrelevante Ereignisse enthalten. 6 Daten zu HCV-Patienten, Genotyp 2 und 3, (therapienaiv) (Gesamtpopulation der FISSION-Studie; Therapieregime Sofosbuvir plus Ribavirin über 12 Wochen) aus der Nutzenbewertung Sofosbuvir (A 14-05) des IQWiG; Anhang B, Tabelle 29. 7 Schlaflosigkeit 31 (12,1) 70 (28,8) Erkrankungen der Haut und des Unterhautzellgewebes Ausschlag 23 (9,0) 43 (17,7) Pruritus 19 (7,4) 42 (17,3) Stoffwechsel und Ernährungsstörungen Appetit vermindert 17 (6,6) 44 (18,1) Skelettmuskulatur-, Bindegewebs- und Knochenerkrankungen Arthralgie 15 (5,9) 35 (14,4) Myalgie 21 (8,2) 40 (16,5) e) In Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapieerfahrenen Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 2) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin: Anhaltspunkt für einen geringen Zusatznutzen. Studienergebnisse nach Endpunkten (FUSION)7 Endpunkt Interventionsgruppe SOF+ RBV [12 Wochen] Patient mit Ereignissen n (%) Mortalität Gesamtmortalität 0 (0) Morbidität SVR 122 Responder Teilpopulation Genotyp 2 (N = 39) 32 (82,1) Teilpopulation Genotyp 2 (ohne Zirrhose) (N = 29) 26 (89,6) Teilpopulation Genotyp 2 (mit Zirrhose) (N = 10) 6 (60,0) 7 Daten zu HCV-Patienten, aus dem Assessment report zu Sovaldi (Procedure No. EMA/H/C/002798/0000), Tabelle 9 und Tabelle 15; FUSION-Studie (Phase III, therapieerfahrene HCV Patienten mit den Genotypen 2 oder 3; Therapieregime Sofosbuvir plus Ribavirin über 12 Wochen oder über 16 Wochen). 8 Gesundheitsbezogene Lebensqualität Keine Angabe von Daten Nebenwirkungen (Gesamtpopulation) Keine Angabe von Daten Studienergebnisse nach Endpunkten (VALENCE)8 Endpunkt Interventionsgruppe SOF+ RBV [12 Wochen] Patient mit Ereignissen n (%) Mortalität Gesamtmortalität Keine Angabe von Daten Morbidität SVR 122 Responder Teilpopulation Genotyp 2 (Therapieerfahren) (N = 41) 37 (90) Teilpopulation Genotyp 2 (Therapieerfahren), (ohne Zirrhose) (N = 33) 30 (91) Teilpopulation Genotyp 2 (Therapieerfahren), (mit Zirrhose) (N = 8) 7 (88) Gesundheitsbezogene Lebensqualität Keine Angabe von Daten Nebenwirkungen (Gesamtpopulation) Keine Angabe von Daten f) In Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven und therapieerfahrenen Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 3) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin: Anhaltspunkt für einen geringen Zusatznutzen. 8 Daten zu HCV-Patienten, aus dem Assessment report zu Sovaldi (Procedure No. EMA/H/C/002798/0000), Tabelle 15; VALENCE-Studie (Phase III, Therapienaive und therapieerfahrene HCV Patienten mit den Genotypen 2 oder 3; Therapieregime Sofosbuvir plus Ribavirin über 12 bzw. 24 Wochen). 9 Studienergebnisse nach Endpunkten (VALENCE)9 Endpunkt Interventionsgruppe SOF+ RBV [24 Wochen] Patient mit Ereignissen n (%) Mortalität Gesamtmortalität Keine Angabe von Daten Morbidität SVR 122 Responder Teilpopulation Genotyp 3 (Therapienaiv) (N = 105) 98 (93) Teilpopulation Genotyp 3 (Therapienaiv), (ohne Zirrhose) (N = 92) 86 (94) Teilpopulation Genotyp 3 (Therapienaiv), (mit Zirrhose) (N = 13) 12 (92) Teilpopulation Genotyp 3 (Therapieerfahren) (N = 145) 112 (77) Teilpopulation Genotyp 3 (Therapieerfahren), (ohne Zirrhose) (N = 100) 85 (85) Teilpopulation Genotyp 3 (Therapieerfahren), (mit Zirrhose) (N = 45) 27 (60) Gesundheitsbezogene Lebensqualität Keine Angabe von Daten Nebenwirkungen (Gesamtpopulation) Keine Angabe von Daten g) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven und therapieerfahrenen Patienten mit chronischer Hepatitis-C- Virus (cHCV) Infektion (Genotyp 3) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin: Ein Zusatznutzen ist nicht belegt. 9 Daten zu HCV-Patienten, aus dem Assessment report zu Sovaldi (Procedure No. EMA/H/C/002798/0000), Tabelle 10 und Tabelle 15; VALENCE-Studie (Phase III, Therapienaive und therapieerfahrene HCV Patienten mit den Genotypen 2 oder 3; Therapieregime Sofosbuvir plus Ribavirin über 12 bzw. 24 Wochen). 10 h) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven und therapieerfahrenen Patienten mit chronischer Hepatitis-C- Virus (cHCV) Infektion (Genotyp 4, 5 und 6) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin: Ein Zusatznutzen ist nicht belegt. i) In Kombination mit Peginterferon alfa + Ribavirin bzw. Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei Patienten mit einer HIV-Koinfektion (therapienaiv, therapieerfahren) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1-6) Zweckmäßige Vergleichstherapie: Duale Therapie (Kombination aus Peginterferon alfa und Ribavirin) Ausmaß und Wahrscheinlichkeit des Zusatznutzens gegenüber Peginterferon alfa + Ribavirin: Anhaltspunkt für einen geringen Zusatznutzen. Studienergebnisse nach Endpunkten (PHOTON-1)10 Endpunkt Interventionsgruppe SOF+ RBV [12 Wochen Therapienaive Patienten; 24 Wochen therapieerfahrene Patienten] Patient mit Ereignissen: n (%) Mortalität Gesamtmortalität Keine Angabe von Daten Morbidität SVR 122 Responder Teilpopulation Genotyp 1 (Therapienaiv) (N = 114) 87 (76) Teilpopulation Genotyp 1 (Therapienaiv), (ohne Zirrhose) (N = 109) 84 (77) 10 Daten zu HCV-Patienten, aus dem Assessment report zu Sovaldi (Procedure No. EMA/H/C/002798/0000), Tabelle 15; PHOTON-Studie (Phase III) nicht randomisiert, offen, parallel, multizentrisch; Therapienaive und therapieerfahrene HCV Patienten mit den Genotypen 1 (nur therapienaiv), 2 oder 3 und HIV-1-Koinfektion; Therapieregime Sofosbuvir plus Ribavirin über 12 bzw. 24 Wochen). 11 Teilpopulation Genotyp 1 (Therapienaiv), (mit Zirrhose) (N = 5) 3 (60) Teilpopulation Genotyp 2 (Therapienaiv) (N = 26) 23 (89) Teilpopulation Genotyp 2 (Therapienaiv), (ohne Zirrhose) (N = 25) 22 (88) Teilpopulation Genotyp 2 (Therapienaiv), (mit Zirrhose) (N = 1) 1 (100) Teilpopulation Genotyp 2 (Therapieerfahren) (N = 15) 14 (93) Teilpopulation Genotyp 2 (Therapieerfahren), (ohne Zirrhose) (N = 13) 12 (92) Teilpopulation Genotyp 2 (Therapieerfahren), (mit Zirrhose) (N = 2) 2 (100) Teilpopulation Genotyp 3 (Therapieerfahren) (N = 13) 12 (92) Teilpopulation Genotyp 3 (Therapieerfahren), (ohne Zirrhose) (N = 8) 8 (100) Teilpopulation Genotyp 3 (Therapieerfahren), (mit Zirrhose) (N = 5) 4 (80) Gesundheitsbezogene Lebensqualität Keine Angabe von Daten Nebenwirkungen Keine Angabe von Daten 12 2. Anzahl der Patienten bzw. Abgrenzung der für die Behandlung infrage kommenden Patientengruppen a) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin + Proteaseinhibitor (Boceprevir oder Telaprevir) bei therapienaiven Patienten ohne Zirrhose mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Anzahl: ca. 14.700 Patienten b) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven Patienten mit Zirrhose mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Anzahl: ca. 600 Patienten c) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin + Proteaseinhibitor (Boceprevir oder Telaprevir) bei therapieerfahrenen Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Anzahl: ca. 43.500 Patienten d) In Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 2) Anzahl: ca. 4.600 Patienten e) In Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapieerfahrenen Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 2) Anzahl: ca. 2.000 Patienten f) In Kombination mit Peginterferon alfa + Ribavirin sowie in Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven und therapieerfahrenen Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 3) Anzahl: ca. 26.700 Patienten g) In Kombination mit Peginterferon alfa + Ribavirin gegenüber Peginterferon alfa + Ribavirin bei therapienaiven und therapieerfahrenen Patienten mit chronischer Hepatitis-C- Virus (cHCV) Infektion (Genotyp 4, 5 und 6) Anzahl: ca. 3.100 Patienten 13 h) In Kombination mit Peginterferon alfa + Ribavirin bzw. Kombination mit Ribavirin gegenüber Peginterferon alfa + Ribavirin bei Patienten mit einer HIV-Koinfektion (therapienaiv, therapieerfahren) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1-6) Anzahl: ca. 4.700 Patienten 3. Anforderungen an eine qualitätsgesicherte Anwendung Die Vorgaben der Fachinformation sind zu berücksichtigen. Die europäische Zulassungs- behörde European Medicines Agency (EMA) stellt die Inhalte der Fachinformation zu Sovaldi® (Wirkstoff: Sofosbuvir) unter folgendem Link frei zugänglich zur Verfügung (letzter Zugriff: 8. Juli 2014): http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_- _Product_Information/human/002798/WC500160597.pdf Die Einleitung und Überwachung der Behandlung mit Sofosbuvir soll durch in der Therapie von Patienten mit chronischer Hepatitis C-Virus Infektion erfahrenen Ärzten erfolgen. 4. Therapiekosten a) Genotyp 1 Behandlungsdauer: Tabelle: therapienaive ohne Zirrhose und therapieerfahrene (mit/ohne Zirrhose) Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patienten- gruppe Bezeichnung der Therapie Behandlungs- modus Anzahl Behandlungen pro Patient pro Jahr Behandlungs- dauer je Behandlung (Tage) Behandlungs- dauer pro Patienten pro Jahr (Tage) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 12 Wochen 84 84 12 84 84 12 Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen11 168 168 24 168 168 24 11 Laut Fachinformation von Sovaldi® (Stand April 2014) ist zu erwägen, die Dauer der Therapie möglicherweise über 12 Wochen hinaus auf bis zu 24 Wochen zu verlängern; dies gilt insbesondere für Subgruppen mit einem oder mehreren prädiktiven Faktoren, die in der Vergangenheit mit niedrigeren Ansprechraten auf interferon-haltige Therapien (z.B. fortgeschrittene Fibrose/Zirrhose, hohe Ausgangsviruslast schwarze Hautfarbe, IL28B-Non-CC-Genotyp, früheres Nichtansprechen auf Peginterferon alfa und Ribavirin) assoziiert waren. http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Product_Information/human/002798/WC500160597.pdf http://www.ema.europa.eu/docs/de_DE/document_library/EPAR_-_Product_Information/human/002798/WC500160597.pdf 14 Zweckmäßige Vergleichstherapie - Tripel Therapie Therapie- naive ohne Zirrhose (Früh- responder)12 Boceprevir +Ribavirin +Peginterferon 3 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 28 Wochen 168 196 28 168 196 28 4 Wochen Ribavirin + Peginterferon danach 24 Wochen Boceprevir + Ribavirin + Peginterferon Therapie- naive und Therapie- erfahrene ohne Zirrhose Boceprevir +Ribavirin +Peginterferon 3 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 224 336 48 224 336 48 4 Wochen Ribavirin + Peginterferon danach 32 Wochen Boceprevir + Ribavirin +Peginterferon danach 12 Wochen Ribavirin + Peginterferon Therapie- erfahrene mit Zirrhose / Null- Responder Boceprevir +Ribavirin +Peginterferon 3 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 308 336 48 308 336 48 4 Wochen Ribavirin + PegInterferon danach 44 Wochen Boceprevir + Ribavirin + Peginterferon Therapie- naive und Relaps- Patienten13 ohne Zirrhose, die frühzeitig auf eine Telaprevir +Ribavirin +Peginterferon 3 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen 84 168 24 84 168 24 12 Wochen Telaprevir + Ribavirin + 12 Patienten mit nicht mehr nachweisbarer HCV-RNA in Woche 8 und 24 (Fachinformation Victrelis®, Stand März 2014). 13 Patienten, die auf eine vorangegangene Therapie mit Interferon und Ribavirin einen Rückfall erlitten haben. 15 Therapie ansprechen14 Peginterferon danach 12 Wochen Ribavirin + Peginterferon Therapienaive (ohne Zirrhose) und Therapie- erfahrene Telaprevir +Ribavirin +Peginterferon 3 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 84 336 48 84 336 48 12 Wochen Telaprevir + Ribavirin + Peginterferon danach 36 Wochen Ribavirin + Peginterferon Zweckmäßige Vergleichstherapie – Duale Therapie Therapienaive ohne Zirrhose (niedrige Ausgangs- viruslast15;16 Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen 168 24 168 24 24 Wochen Ribavirin + Peginterferon Therapienaive (ohne Zirrhose) und Therapie- erfahrene17 +Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 336 48 336 48 48 Wochen Ribavirin + Peginterferon Therapie- erfahrene18 +Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 72 Wochen 504 72 504 72 (in einem Behandlungs zyklus von 72 Wochen) 72 Wochen Ribavirin + Peginterferon 14 Patienten mit nicht mehr nachweisbarer HCV-RNA in Woche 4 und 12 (Fachinformation Incivo®, Stand Dezember 2013). 15 Patienten vom Genotyp 1 mit niedriger Ausgangsviruslast (LVL) (≤ 800.000 I.E./ml), die bis Woche 4 HCV-RNA negativ werden und bis Woche 24 negativ bleiben. 16 Eine Gesamtbehandlungsdauer von 24 Wochen kann mit einem erhöhten Rückfallrisiko verbunden sein. Bei diesen Patienten sollte die Verträglichkeit der Kombinationstherapie und zusätzliche prognostische Faktoren wie der Fibrosegrad berücksichtigt werden. 17 Behandlung Therapieerfahrener mit der Kombination Rebetol® / Ribavirin generisch und Pegintron®: laut Fachinformation 48 Wochen Behandlungsdauer. 18 Behandlung Therapieerfahrener / Genotyp 1 mit der Kombination Copegus® und Pegasys®: laut Fachinformation 72 Wochen Behandlungsdauer. 16 Tabelle: therapienaive Patienten (mit Zirrhose) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patienten- gruppe Bezeichnung der Therapie Behandlungs- modus Anzahl Behandlungen pro Patient pro Jahr Behandlungs- dauer je Behandlung (Tage) Behandlungs- dauer pro Patienten pro Jahr (Tage) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 12 Wochen 84 84 12 84 84 12 Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen11 168 168 24 168 168 24 Zweckmäßige Vergleichstherapie – Duale Therapie Therapienaive (mit Zirrhose) +Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 336 48 336 48 48 Wochen Ribavirin + Peginterferon Verbrauch: Tabelle: therapienaive ohne Zirrhose und therapieerfahrene Patienten (mit/ohne Zirrhose) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin + Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 84 Tab. 420 Tab. 12 Fs Sofosbuvir + Ribavirin + Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 168 Tab. 840 Tab. 24 Fs Zweckmäßige Vergleichstherapie – Tripel Therapie Therapienaive ohne Zirrhose (Früh- Boceprevir + Ribavirin 2.400 mg (3 x [4 x 200 mg]) 1.000 mg19 336 Tab. 168 Tab. 2.016 Tab. 980 Tab. 19 Körpergewicht < 75 kg 17 Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) responder)12 + Peginterferon (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 12 (4) Fs 28 Fs Therapienaive und Therapie- erfahrene ohne Zirrhose Boceprevir + Ribavirin + Peginterferon 2.400 mg (3 x [4 x 200 mg]) 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 336 Tab. 168 Tab. 12 Fs 2.688 Tab. 1.680 Tab. 48 Fs Therapie- erfahrene mit Zirrhose / Null- Responder Boceprevir + Ribavirin + Peginterferon 2.400 mg (3 x [4 x 200 mg]) 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 336 Tab. 168 Tab. 12 Fs 3.696 Tab. 1.680 Tab. 48 Fs Therapienaive und Relaps- Patienten13 ohne Zirrhose, die frühzeitig auf eine Therapie ansprechen14 Telaprevir + Ribavirin +Peginterferon 2.250 mg (3 x [2 x 375 mg]) 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 168 Tab. 12 Fs 504 Tab. 840 Tab. 24 Fs Therapienaive (ohne Zirrhose) und Therapie- erfahrene Telaprevir + Ribavirin + Peginterferon 2.250 mg (3 x [2 x 375 mg]) 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 168 Tab. 12 Fs 504 Tab. 1.680 Tab. 48 Fs Zweckmäßige Vergleichstherapie – Duale Therapie Therapienaive ohne Zirrhose (niedrige Ausgangsvirus- last)15,16 Ribavirin +Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 840 Tab. 24 Fs Therapienaive ohne Zirrhose Ribavirin + Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 1.680 Tab. 48 Fs Therapie- erfahrene17 Ribavirin + Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 100 µg19 168 Tab. 12 Fs 1.680 Tab. 48 Fs Therapie- erfahrene18 Ribavirin + Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 2.520 Tab. 72 Fs 18 Tabelle: therapienaive Patienten (mit Zirrhose) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) Zu bewertendes Arzneimittel Sofosbuvir + Ribavirin + Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 84 Tab. 420 Tab. 12 Fs Sofosbuvir + Ribavirin + Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 168 Tab. 840 Tab. 24 Fs Zweckmäßige Vergleichstherapie – Duale Therapie Therapie- naive (mit Zirrhose) Ribavirin + Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 1.680 Tab. 48 Fs Kosten: Kosten der Arzneimittel: Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte Sofosbuvir (Sovaldi®) 19.999,46 € 18.858,76 € [1,80 € 20; 1.138,90 € 21] Boceprevir (Victrelis®) 3.146,09 €22 3144,29 € [1,80 € 20] Telaprevir (Incivo® 375mg) 9.663,53 €22 9.661,73 € [1,80 € 20] Ribavirin (Copegus® 200 mg) 1.004,21 € (168 Stück) 259,30 € (42 Stück) 822,24 € [1,80 € 20; 180,17 € 21] 212,45 € [1,80 € 13; 45,05 € 21] 20 Rabatt nach § 130 SGB V. 21 Rabatt nach § 130a SGB V. 22 Abgabepreis nach § 78 Abs. 3a AMG in Verbindung mit § 130 b SGB V. 19 Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte Ribavirin (generisch 200 mg) 763,24 € 725,74 € [1,80 € 20; 35,70 € 21] Peginterferon (Pegasys® 180 µg) 3.362,30 € (12 Stück) 1.147,34 € (4 Stück) 3.052,34 € [1,80 € 13; 308,16 € 21] 1.042,82 € [1,80 € 20; 102,72 € 21] Peginterferon (PegIntron® 100 µg) 3.312,04 € 3.040,85 € [1,80 € 20; 269,39€ 21] Stand Lauer-Taxe: 1. Juni 2014 Kosten für zusätzlich notwendige GKV-Leistungen: Tabelle: Therapienaive Patienten ohne Zirrhose und therapieerfahrene Patienten (mit/ohne Zirrhose) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patientengruppe Bezeichnung der Therapie Bezeichnung der zusätzlich notwendigen GKV- Leistung Anzahl der zusätzlich notwendigen GKV-Leistung je Zyklus e.c. Anzahl der zusätzlich notwendigen GKV-Leistung pro Patient und Jahr Kosten pro Einheit Zu bewertendes Arzneimittel - Sofosbuvir +Ribavirin +Peginterferon (12 sowie 24 Wochen11) keine - - - Zweckmäßige Vergleichstherapie – Tripel Therapie Therapienaive ohne Zirrhose (Frühresponder)12 Boceprevir + Ribavirin +Peginterferon (28 Wochen) Bestimmung des HCV- RNA Spiegels 3 x in Behandlungs- woche 8, 12, 24 3 89,50 € Therapienaive und Therapieerfahrene ohne Zirrhose Boceprevir + Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV- RNA Spiegels 3 x in Behandlungs- woche 8, 12, 24 3 89,50 € Therapieerfahrene mit Zirrhose / Null- Responder Boceprevir + Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV- RNA Spiegels 3 x in Behandlungs- woche 8, 12, 24 3 89,50 € Therapienaive und Relaps-Patienten13 ohne Zirrhose, die frühzeitig auf eine Therapieansprechen14 Telaprevir + Ribavirin +Peginterferon (24 Wochen) Bestimmung des HCV- RNA Spiegels 2 x in Behandlungs- woche 4, 12 2 89,50 € 20 Therapienaive (ohne Zirrhose) und Therapieerfahrene Telaprevir + Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV- RNA Spiegels 4 x in Behandlungs- woche 4, 12, 24, 36 4 89,50 € Zweckmäßige Vergleichstherapie – Duale Therapie Therapienaive ohne Zirrhose (niedrige Ausgangsviruslast15,16) Ribavirin +Peginterferon (24 Wochen) Bestimmung des HCV- RNA Spiegels 2 x in Behandlungs- woche 4, 24 2 89,50 € Therapienaive (ohne Zirrhose); Therapieerfahrene17 Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV- RNA Spiegels 1 x in Behandlungs- woche 4 bzw.12 1 89,50 € Therapieerfahrene18 Ribavirin +Peginterferon (72 Wochen) Bestimmung des HCV- RNA Spiegels 1 x in Behandlungs- woche 12 1 89,50 € Tabelle: therapienaive Patienten mit Zirrhose mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patientengruppe Bezeichnung der Therapie Bezeichnung der zusätzlich notwendigen GKV-Leistung Anzahl der zusätzlich notwendigen GKV-Leistung je Zyklus e.c. Anzahl der zusätzlich notwendigen GKV-Leistung pro Patient und Jahr Kosten pro Einheit Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon (12 sowie 24 Wochen11) keine - - - Zweckmäßige Vergleichstherapie – Duale Therapie Therapienaive (mit Zirrhose) Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV- RNA Spiegels 1 x in Behandlungs- woche 4 - 89,50 € Jahrestherapiekosten: Tabelle: therapienaive ohne Zirrhose und therapieerfahrene Patienten (mit/ohne Zirrhose) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (12 Wochen) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Peginterferon 3.052,34 € 21 Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (24 Wochen11) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zweckmäßige Vergleichstherapie: Boceprevir + Ribavirin + Peginterferon (28 Wochen) Therapienaive ohne Zirrhose (Frühresponder)12 Boceprevir 18.865,74 € Ribavirin 4.933,44 € Peginterferon 7.147,50 € Zusätzlich notwendige GKV- Leistung 268,50 € Zweckmäßige Vergleichstherapie: Boceprevir + Ribavirin + Peginterferon (48 Wochen) Therapienaive und Therapie- erfahrene ohne Zirrhose Boceprevir 25.154,32 € Ribavirin 8.222,40 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 268,50 € Zweckmäßige Vergleichstherapie: Boceprevir + Ribavirin + Peginterferon (48 Wochen) Therapieerfahrene mit Zirrhose / Null-Responder Boceprevir 34.587,19 € Ribavirin 8.222,40 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 268,50 € Zweckmäßige Vergleichstherapie: Telaprevir + Ribavirin + Peginterferon (24 Wochen) Therapienaive und Relaps- Patienten13 ohne Zirrhose, die frühzeitig auf eine Therapie ansprechen14 Telaprevir 28.985,19 € Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zusätzlich notwendige GKV- Leistung 179,00 € Zweckmäßige Vergleichstherapie: Telaprevir + Ribavirin + Peginterferon (48 Wochen) Therapienaive (ohne Zirrhose) und Therapieerfahrene Telaprevir 28.985,19 € Ribavirin 8.222,40 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 358,00 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (24 Wochen) Therapienaive (ohne Zirrhose) (niedrige Ausgangsviruslast)15;16 Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zusätzlich notwendige GKV- Leistung 179,00 € 22 Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) Therapienaive (ohne Zirrhose) Ribavirin 8.222,40 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 89,50 € Therapieerfahrene17 Ribavirin 7.257,40 € Peginterferon 12.163,40 € Zusätzlich notwendige GKV- Leistung 89,50 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (72 Wochen) Therapieerfahrene18 Ribavirin 12.333,60 € Peginterferon 18.314,04 € Zusätzlich notwendige GKV- Leistung 89,50 € Tabelle: therapienaive Patienten (mit Zirrhose) mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 1) Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (12 Wochen) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Peginterferon 3.052,34 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (24 Wochen11) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) Therapienaive (mit Zirrhose) Ribavirin 8.222,40 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 89,50 € 23 b) Genotyp 2 Behandlungsdauer Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 2) Population bzw. Patientengrup pe Bezeichnung der Therapie Behandlungs- modus Anzahl Behandlungen pro Patient pro Jahr Behandlungs- dauer je Behandlung (Tage) Behandlungs- dauer pro Patienten pro Jahr (Tage) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin 1 x täglich 2 x täglich Ein Behandlungs- zyklus von 12 Wochen 84 84 84 84 Sofosbuvir +Ribavirin 1 x täglich 2 x täglich Ein Behandlungs- zyklus von 24 Wochen11 168 168 168 168 Zweckmäßige Vergleichstherapie Therapienaive (niedrige Ausgangs- viruslast)23;24 Ribavirin + Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 16 Wochen 112 16 112 16 16 Wochen Ribavirin + Peginterferon Therapienaive Ribavirin + Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen 168 24 168 24 24 Wochen Ribavirin + Peginterferon Therapie- erfahrene Ribavirin + Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 336 48 336 48 48 Wochen Ribavirin + Peginterferon 23 Patienten vom Genotyp 2 und 3 mit niedriger Ausgangsviruslast (LVL) (≤ 800.000 I.E./ml), die bis Woche 4 HCV-RNA negativ geworden sind und bis Woche 16 negativ bleiben. 24 Insgesamt kann eine Behandlungsdauer von 16 Wochen mit einer geringeren Ansprechwahrscheinlichkeit verbunden sein und hat ein höheres Rückfallrisiko als eine Behandlung über 24 Wochen. Bei diesen Patienten sollte die Verträglichkeit der Kombinationstherapie und zusätzliche prognostische Faktoren wie der Fibrosegrad berücksichtigt werden, wenn eine Abweichung von der üblichen Behandlungsdauer von 24 Wochen in Betracht gezogen wird. 24 Verbrauch: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 2) Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) Zu bewertendes Arzneimittel Sofosbuvir + Ribavirin 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 28 Tab. 168 Tab. 84 Tab. 420 Tab. Sofosbuvir + Ribavirin 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 28 Tab. 168 Tab. 168 Tab. 840 Tab. Zweckmäßige Vergleichstherapie Therapienaive (niedrige Ausgangs- viruslast)23;24 Ribavirin + Peginterferon 800 mg (2 x 400mg) 180 µg 56 Tab. 12 Fs 224 Tab. 16 Fs Therapienaive Ribavirin + Peginterferon 800 mg (1 x [2 x 200 mg], 1 x [2 x 200 mg]) 180 µg 168 Tab. 12 Fs 672 Tab. 24 Fs Therapie- erfahrene Ribavirin + Peginterferon 800 mg (1 x [2 x 200 mg], 1 x [2 x 200 mg]) 180 µg 168 Tab. 12 Fs 1.344 Tab. 48 Fs Kosten: Kosten der Arzneimittel: Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte Sofosbuvir (Sovaldi®) 19.999,46 € 18.858,76 € [1,80 € 20; 1138,90 € 21] Ribavirin (Copegus® 200 mg) 1.004,21 € (168 Stück) 259,30 € (42 Stück) 822,24 € [1,80 € 20; 180,17 € 21] 212,45 € [1,80 € 20; 45,05 € 21] Ribavirin (Copegus® 400 mg) 673,14 € (56 Stück) 551,23 € [1,80 € 20; 120,11 € 21] Peginterferon 33.62,30 € (12 Stück) 3.052,34 € [1,80 € 20; 308,16 € 21] 25 Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte (Pegasys® 180 µg) 1.147,34 € (4 Stück) 1042,82 € [1,80 € 20; 102,72 € 21] Stand Lauer-Taxe: 1. Juni 2014 Kosten für zusätzlich notwendige GKV-Leistungen: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 2) Population bzw. Patientengruppe Bezeichnung der Therapie Bezeichnung der zusätzlich notwendigen GKV-Leistung Anzahl der zusätzlich notwendigen GKV-Leistung je Zyklus e.c. Anzahl der zusätzlich notwendigen GKV-Leistung pro Patient und Jahr Kosten pro Einheit Zu bewertendes Arzneimittel - Sofosbuvir +Ribavirin (12 sowie 24 Wochen11) keine - - - Zweckmäßige Vergleichstherapie Therapienaive (niedrige Ausgangsviruslast)23;24 Ribavirin +Peginterferon (16 Wochen) Bestimmung des HCV-RNA Spiegels 2 x in Behandlungs- woche 4, 16 2 89,50 € Therapienaive Ribavirin +Peginterferon (24 Wochen) Bestimmung des HCV-RNA Spiegels 1 x in Behandlungs- woche 4 1 89,50 € Therapieerfahrene Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV-RNA Spiegels 1 x in Behandlungs- woche.12 1 89,50 € Jahrestherapiekosten: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C- Virus (cHCV) Infektion (Genotyp 2) Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin (12 Wochen) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin (24 Wochen11) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € 26 Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (16 Wochen) Therapienaive (niedrige Ausgangsviruslast)23;24 Ribavirin 2.204,92 € Peginterferon 4.095,16 € Zusätzlich notwendige GKV- Leistung 179,00 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (24 Wochen) Therapienaive Ribavirin 3.288,96 € Peginterferon 6.104,68 € Zusätzlich notwendige GKV- Leistung 89,50 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) Therapieerfahrene Ribavirin 6.577,92 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 89,50 € c) Genotyp 3 Behandlungsdauer Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 3) Population bzw. Patienten- gruppe Bezeichnung der Therapie Behandlungs- modus Anzahl Behandlungen pro Patient pro Jahr Behandlungs- dauer je Behandlung (Tage) Behandlungs- dauer pro Patienten pro Jahr (Tage) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs -zyklus von 12 Wochen 84 84 12 84 84 12 Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs -zyklus von 24 Wochen11 168 168 24 168 168 24 Sofosbuvir +Ribavirin 1 x täglich 2 x täglich Ein Behandlungs -zyklus von 24 Wochen 168 168 168 168 Zweckmäßige Vergleichstherapie Therapienaive (niedrige Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs 112 16 112 16 27 Ausgangs- viruslast)23;24 16 Wochen Ribavirin + Peginterferon -zyklus von 16 Wochen Therapienaive Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs -zyklus von 24 Wochen 168 24 168 24 24 Wochen Ribavirin + Peginterferon Therapie- erfahrene Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs -zyklus von 48 Wochen 336 48 336 48 48 Wochen Ribavirin + Peginterferon Verbrauch: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 3) Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) Zu bewertendes Arzneimittel Sofosbuvir + Ribavirin +Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 84 Tab. 420 Tab. 12 Fs Sofosbuvir + Ribavirin + Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 168 Tab. 840 Tab. 24 Fs Sofosbuvir + Ribavirin 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 28 Tab. 168 Tab. 168 Tab. 840 Tab. Zweckmäßige Vergleichstherapie Therapienaive (niedrige Ausgangs- viruslast)23;24 Ribavirin + Peginterferon 800 mg (2 x 400mg) 180 µg 56 Tab. 12 Fs 224 Tab. 16 Fs Therapienaive Ribavirin + Peginterferon 800 mg (1 x [2 x 200 mg], 1 x [2 x 200 mg]) 180 µg 168 Tab. 12 Fs 672 Tab. 24 Fs 28 Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) Therapie- erfahrene Ribavirin + Peginterferon 800 mg (1 x [2 x 200 mg], 1 x [2 x 200 mg]) 180 µg 168 Tab. 12 Fs 1.344 Tab. 48 Fs Kosten: Kosten der Arzneimittel: Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte Sofosbuvir (Sovaldi®) 19.999,46 € 18.858,76 € [1,80 € 20; 1138,90 € 21] Ribavirin (Copegus® 200 mg) 1.004,21 € (168 Stück) 259,30 € (42 Stück) 822,24 € [1,80 € 20; 180,17 € 21] 212,45 € [1,80 € 20; 45,05 € 21] Ribavirin (Copegus® 400 mg) 673,14 € (56 Stück) 551,23 € [1,80 € 20; 120,11 € 21] Peginterferon (Pegasys® 180 µg) 3.362,30 € (12 Stück) 1.147,34 € (4 Stück) 3.052,34 € [1,80 € 20; 308,16 € 21] 1.042,82 € [1,80 € 20; 102,72 € 21] Stand Lauer-Taxe: 1. Juni 2014 Kosten für zusätzlich notwendige GKV-Leistungen: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 3) Population bzw. Patientengruppe Bezeichnung der Therapie Bezeichnung der zusätzlich notwendigen GKV- Leistung Anzahl der zusätzlich notwendigen GKV-Leistung je Zyklus e.c. Anzahl der zusätzlich notwendigen GKV-Leistung pro Patient und Jahr Kosten pro Einheit Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon (12 sowie 24 Wochen11) keine - - - - Sofosbuvir +Ribavirin keine - - - 29 (24 Wochen) Zweckmäßige Vergleichstherapie Therapienaive (niedrige Ausgangsviruslast)23;24 Ribavirin +Peginterferon (16 Wochen) Bestimmung des HCV- RNA Spiegels 2 x in Behandlungs- woche 4,16 2 89,50 € Therapienaive Ribavirin +Peginterferon (24 Wochen) Bestimmung des HCV- RNA Spiegels 1 x in Behandlungs- woche 4 1 89,50 € Therapieerfahrene Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV- RNA Spiegels 1 x in Behandlungs- woche.12 1 89,50 € Jahrestherapiekosten: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 3) Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (12 Wochen) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Peginterferon 3.052,34 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (24 Wochen11) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin (24 Wochen) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (16 Wochen) Therapienaive (niedrige Ausgangsviruslast)23;24 Ribavirin 2.204,92 € Peginterferon 4.095,16 € Zusätzlich notwendige GKV- Leistung 179,00 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (24 Wochen) Therapienaive Ribavirin 3.288,96 € Peginterferon 6.104,68 € Zusätzlich notwendige GKV- Leistung 89,50 € 30 Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) Therapieerfahrene Ribavirin 6.577,92 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 89,50 € d) Genotyp 4 Behandlungsdauer Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 4) Population bzw. Patientengrup pe Bezeichnung der Therapie Behandlungs- modus Anzahl Behandlungen pro Patient pro Jahr Behandlungs- dauer je Behandlung (Tage) Behandlungs- dauer pro Patienten pro Jahr (Tage) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 12 Wochen 84 84 12 84 84 12 Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen11 168 168 24 168 168 24 Zweckmäßige Vergleichstherapie Therapienaive (Früh- responder)25; 26 Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen 168 24 168 24 24 Wochen Ribavirin + Peginterferon Therapienaive und Therapie- erfahrene Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 336 48 336 48 48 Wochen Ribavirin + Peginterferon 25 Patienten, die bis Woche 4 HCV-RNA-negativ werden und bis Woche 24 HCV-RNA-negativ bleiben. 26 Eine Gesamtbehandlungsdauer von 24 Wochen kann mit einem erhöhten Ruckfallrisiko verbunden sein als eine Behandlung über 48 Wochen. Bei diesen Patienten sollte die Verträglichkeit der Kombinationstherapie und zusätzliche prognostische Faktoren wie der Fibrosegrad berücksichtigt werden. 31 Verbrauch: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 4) Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 84 Tab. 420 Tab. 12 Fs Sofosbuvir +Ribavirin +Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 168 Tab. 840 Tab. 24 Fs Zweckmäßige Vergleichstherapie Therapienaive (Früh- responder)25;26 Ribavirin +Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 840 Tab. 24 Fs Therapie- naive, Therapie- erfahrene Ribavirin +Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 1.680 Tab. 48 Fs Kosten: Kosten der Arzneimittel: Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte Sofosbuvir (Sovaldi®) 19.999,46 € 18.858,76 € [1,80 € 20; 1138,90 € 21] Ribavirin (Copegus® 200 mg) 1.004,21 € (168 Stück) 259,30 € (42 Stück) 822,24 € [1,80 € 20; 180,17 € 21] 212,45 € [1,80 € 20; 45,05 € 21] Peginterferon (Pegasys® 180 µg) 3.362,30 € (12 Stück) 3.052,34 € [1,80 € 20; 308,16 € 21] Stand Lauer-Taxe: 1. Juni 2014 32 Kosten für zusätzlich notwendige GKV-Leistungen: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 4) Population bzw. Patientengruppe Bezeichnung der Therapie Bezeichnung der zusätzlich notwendigen GKV-Leistung Anzahl der zusätzlich notwendigen GKV-Leistung je Zyklus e.c. Anzahl der zusätzlich notwendigen GKV-Leistung pro Patient und Jahr Kosten pro Einheit Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon (12 sowie 24 Wochen11) keine - - - Zweckmäßige Vergleichstherapie Therapienaive (Frühresponder)25;26 Ribavirin +Peginterferon (24 Wochen) Bestimmung des HCV-RNA Spiegels 2 x in Behandlungs- woche 4, 24 2 89,50 € Therapienaive Therapieerfahrene Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV-RNA Spiegels 1 x in Behandlungs- woche 4 bzw.12 1 89,50 € Jahrestherapiekosten: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 4) Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (12 Wochen) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Peginterferon 3.052,34 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (24 Wochen11) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (24 Wochen) Therapienaive (Frühresponder)25;26 Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zusätzlich notwendige GKV- Leistung 179,00 € 33 Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) Therapienaive und Therapieerfahrene Ribavirin 8.222,40 € Peginterferon 12.209,36 € Zusätzlich notwendige GKV- Leistung 89,50 € e) Genotyp 5 oder 6 Behandlungsdauer Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 5 oder 6) Population bzw. Patienten- gruppe Bezeichnung der Therapie Behandlungs- modus Anzahl Behandlungen pro Patient pro Jahr Behandlungs- dauer je Behandlung (Tage) Behandlungs- dauer pro Patienten pro Jahr Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 12 Wochen 84 84 12 84 84 12 Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen11 168 168 24 168 168 24 Zweckmäßige Vergleichstherapie Therapienaive und Therapie- erfahrene +Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 336 48 336 48 48 Wochen Ribavirin + Peginterferon 34 Verbrauch: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 5 oder 6) Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrauch (Tabletten; Spritzen) Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 84 Tab. 420 Tab. 12 Fs Sofosbuvir +Ribavirin +Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 168 Tab. 840 Tab. 24 Fs Zweckmäßige Vergleichstherapie Therapie- naive, Therapie- erfahrene Ribavirin + Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 1.680 Tab. 48 Fs Kosten: Kosten der Arzneimittel: Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte Sofosbuvir (Sovaldi®) 19.999,46 € 18.858,76 € [1,80 € 20; 1138,90 € 21] Ribavirin (Copegus® 200 mg) 1004,21 € (168 Stück) 259,30 € (42 Stück) 822,24 € [1,80 € 20; 180,17 € 21] 212,45 € [1,80 € 20; 45,05 € 21] Peginterferon (Pegasys® 180 µg) 3.362,30 € (12 Stück) 3.052,34 € [1,80 € 20; 308,16 € 21] Stand Lauer-Taxe: 1. Juni 2014 35 Kosten für zusätzlich notwendige GKV-Leistungen: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 5,6) Population bzw. Patientengruppe Bezeichnung der Therapie Bezeichnung der zusätzlich notwendigen GKV-Leistung Anzahl der zusätzlich notwendigen GKV-Leistung je Zyklus e.c. Anzahl der zusätzlich notwendigen GKV-Leistung pro Patient und Jahr Kosten pro Einheit Zu bewertendes Arzneimittel Sofosbuvir +Ribavirin +Peginterferon (12 sowie 24 Wochen11) keine - - - Zweckmäßige Vergleichstherapie Therapienaive Ribavirin +Peginterferon (48 Wochen) keine - - - Therapieerfahrene Ribavirin +Peginterferon (48 Wochen) Bestimmung des HCV-RNA Spiegels 1 x in Behandlungs- woche 12 1 89,50 € Jahrestherapiekosten: Tabelle: therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion (Genotyp 5 oder 6) Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (12 Wochen) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Peginterferon 3.052,34 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (24 Wochen11) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) Therapienaive Ribavirin 8.222,40 € Peginterferon 12.209,36 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) Therapieerfahrene Ribavirin 8.222,40 € Peginterferon 12.209,36 € 36 Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zusätzlich notwendige GKV- Leistung 89,50 € f) Therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion und einer HIV Koinfektion (Genotypen 1-6) Behandlungsdauer Tabelle: Therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion und einer HIV Koinfektion (Genotypen 1-6) Population bzw. Patienten- gruppe Bezeichnung der Therapie Behandlungs- modus Anzahl Behandlungen pro Patient pro Jahr Behandlungs- dauer je Behandlung (Tage) Behandlungs- dauer pro Patienten pro Jahr Zu bewertendes Arzneimittel HCV/HIV Koinfektion (Genotyp 1,3) Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 12 Wochen 84 84 12 84 84 12 HCV/HIV Koinfektion (Genotyp 1,3) Sofosbuvir +Ribavirin +Peginterferon 1 x täglich 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 24 Wochen11 168 168 24 168 168 24 HCV/HIV Koinfektion (Genotyp 2) Sofosbuvir +Ribavirin 1 x täglich 2 x täglich Ein Behandlungs- zyklus von 12 Wochen 84 84 84 84 HCV/HIV Koinfektion (Genotyp 211,3) Sofosbuvir +Ribavirin 1 x täglich 2 x täglich Ein Behandlungs- zyklus von 24 Wochen 168 168 168 168 Zweckmäßige Vergleichstherapie HCV/HIV Koinfektion (Genotyp 1-6) Ribavirin +Peginterferon 2 x täglich 1 x wöchentlich Ein Behandlungs- zyklus von 48 Wochen 336 48 336 48 48 Wochen Ribavirin + Peginterferon 37 Verbrauch: Tabelle: Therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion und einer HIV Koinfektion (Genotypen 1-6) Population bzw. Patienten- gruppe Bezeichnung der Therapie Dosierung pro Tag; Wirkstärke (mg) Menge pro Packung (Tabletten; Spritzen) Jahresdurch- schnittsverbrau ch (Tabletten; Spritzen) Zu bewertendes Arzneimittel HCV/HIV Koinfektion (Genotyp 1,3) Sofosbuvir +Ribavirin +Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 84 Tab. 420 Tab. 12 Fs HCV/HIV Koinfektion (Genotyp 1,3) Sofosbuvir +Ribavirin +Peginterferon 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 28 Tab. 168 Tab. 12 Fs 168 Tab. 840 Tab. 24 Fs HCV/HIV Koinfektion (Genotyp 2) Sofosbuvir +Ribavirin 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 28 Tab. 168 Tab. 84 Tab. 420 Tab. HCV/HIV Koinfektion (Genotyp 2,3) Sofosbuvir +Ribavirin 400 mg 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 28 Tab. 168 Tab. 168 Tab. 840 Tab. Zweckmäßige Vergleichstherapie HCV/HIV Koinfektion (Genotyp 1-6) Ribavirin + Peginterferon 1.000 mg19 (1 x [2 x 200 mg], 1 x [3 x 200 mg]) 180 µg 168 Tab. 12 Fs 1.680 Tab. 48 Fs Kosten: Kosten der Arzneimittel: Bezeichnung der Therapie Kosten (Apothekenabgabepreis) Kosten nach Abzug gesetzlich vorgeschriebener Rabatte Sofosbuvir (Sovaldi®) 19.999,46 € 18.858,76 € [1,80 € 20; 1138,90 € 21] Ribavirin (Copegus® 200 mg) 1.004,21 € (168 Stück) 259,30 € (42 Stück) 822,24 € [1,80 € 20; 180,17 € 21] 212,45 € [1,80 € 20; 45,05 € 21] Peginterferon (Pegasys® 180 µg) 3.362,30 € (12 Stück) 3.052,34 € [1,80 € 20; 308,16 € 21] Stand Lauer-Taxe: 1. Juni 2014 38 Kosten für zusätzlich notwendige GKV-Leistungen: entfällt Jahrestherapiekosten: Tabelle: Therapienaive und therapieerfahrene Patienten mit chronischer Hepatitis-C-Virus (cHCV) Infektion und einer HIV Koinfektion (Genotypen 1-6) Population bzw. Patienten- gruppe Bezeichnung der Therapie Jahrestherapiekosten pro Patient Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (12 Wochen) HCV/HIV Koinfektion (Genotyp 1,3) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Peginterferon 3.052,34 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin + Peginterferon (24 Wochen11) HCV/HIV Koinfektion (Genotyp 1,3) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Peginterferon 6.104,68 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin (12 Wochen) HCV/HIV Koinfektion (Genotyp 2) Sofosbuvir 56.576,28 € Ribavirin 2.069,38 € Zu bewertendes Arzneimittel: Sofosbuvir + Ribavirin (24 Wochen) HCV/HIV Koinfektion (Genotyp 211,3) Sofosbuvir 113.152,56 € Ribavirin 4.111,20 € Zweckmäßige Vergleichstherapie: Ribavirin + Peginterferon (48 Wochen) HCV/HIV Koinfektion (Genotyp 1-6) Ribavirin 8.222,40 € Peginterferon 12.209,36 € 39 II. Inkrafttreten 1. Der Beschluss tritt mit Wirkung vom Tag seiner Veröffentlichung im Internet auf den Internetseiten des Gemeinsamen Bundesausschusses am 17. Juli 2014 in Kraft. 2. Die Geltungsdauer des Beschlusses ist bis zum 15. Juli 2016 befristet. Die Tragenden Gründe zu diesem Beschluss werden auf den Internetseiten des Gemeinsamen Bundesausschusses unter www.g-ba.de veröffentlicht. Berlin, den 17. Juli 2014 Gemeinsamer Bundesausschuss gemäß § 91 SGB V Der Vorsitzende Hecken http://www.g-ba.de/ I. Die Anlage XII wird in alphabetischer Reihenfolge um den Wirkstoff Sofosbuvir wie folgt ergänzt: 1. Zusatznutzen des Arzneimittels im Verhältnis zur zweckmäßigen Vergleichstherapie 2. Anzahl der Patienten bzw. Abgrenzung der für die Behandlung infrage kommenden Patientengruppen 3. Anforderungen an eine qualitätsgesicherte Anwendung 4. Therapiekosten II. Inkrafttreten 1. Der Beschluss tritt mit Wirkung vom Tag seiner Veröffentlichung im Internet auf den Internetseiten des Gemeinsamen Bundesausschusses am 17. Juli 2014 in Kraft. 2. Die Geltungsdauer des Beschlusses ist bis zum 15. Juli 2016 befristet.